Pain sensitisation and the risk of poor outcome following physiotherapy for patients with moderate to severe knee osteoarthritis: protocol for a prospective cohort study Has postoperative pain been eradicated? Characterisation of capsaicin-induced mechanical hyperalgesia as a marker for altered nociceptive processing in patients with rheumatoid arthritis A randomised double blind trial of the effect of pre-emptive epidural ketamine on persistent pain after lower limb amputation Effects of amitriptyline and intra-oral device appliance on clinical and laser-evoked potentials features in chronic tension-type headache Prodromal schizophrenia in primary care: a randomised sensitisation study. Influence of Centrally Mediated Symptoms on Postoperative Pain in Osteoarthritis Patients Undergoing Total Knee Arthroplasty: A Prospective Observational Evaluation. Duloxetine for the management of pain in older adults with knee osteoarthritis: randomised placebo-controlled trial. MR imaging of erosions in interphalangeal joint osteoarthritis: is all osteoarthritis erosive? Neuropathic pain symptoms on the modified painDETECT correlate with signs of central sensitization in knee osteoarthritis. A pilot study of the effectiveness of guided imagery with progressive muscle relaxation to reduce chronic pain and mobility difficulties of osteoarthritis. The effectiveness of self‐management educational interventions for osteoarthritis of the knee Long-term opioid use in non-cancer pain. Laser-evoked potential habituation and central sensitization symptoms in childhood migraine Gabapentin for refractory chronic cough: a randomised, double-blind, placebo-controlled trial The Centralization Phenomenon: Its Usefulness as a Predictor of Outcome in Conservative Treatment of Chronic Low Back Pain (A Pilot Study) The effect of pregabalin or duloxetine on arthritis pain: a clinical and mechanistic study in people with hand osteoarthritis Open pilot study of ultrasound-guided intra-articular injection of hylan G-F 20 (Synvisc) in the treatment of symptomatic hip osteoarthritis Evaluation of GW406381 for treatment of osteoarthritis of the knee: two randomized, controlled studies. Effect of ketamine on endogenous pain modulation in healthy volunteers Depression and osteoarthritis. Lack of efficacy of acetaminophen in treating symptomatic knee osteoarthritis: a randomized, double-blind, placebo-controlled comparison trial with diclofenac sodium. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4)
Introduction Pain is the dominant symptom of knee osteoarthritis ( OA ) , and recent evidence suggests factors outside of local joint pathology , such as pain sensitisation , can contribute significantly to the pain experience . It is unknown how pain sensitisation influences outcomes from commonly employed interventions such as physiotherapy . The aims of this study are , first , to provide a comprehensive description of the somatosensory characteristics of people with pain associated with knee OA . Second , we will investigate if indicators of pain sensitisation in patients with knee osteoarthritis are predictive of non-response to physiotherapy . Methods and analysis This is a multicentre prospect i ve cohort study with 140 participants . Eligible patients with moderate to severe symptomatic knee osteoarthritis will be identified at outpatient orthopaedic and rheumatology clinics . A baseline assessment will provide a comprehensive description of the somatosensory characteristics of each participant by means of clinical examination , quantitative sensory testing , and vali date d question naires measuring pain and functional capacity . Participants will then undergo physiotherapy treatment . The primary outcome will be non-response to physiotherapy on completion of the physiotherapy treatment programme as defined by the Osteoarthritis Research Society International treatment responder criteria . A principal component analysis will identify measures related to pain sensitisation to include in the predictive model . Regression analyses will explore the relationship between responder status and pain sensitisation while accounting for confounders . Ethics and dissemination This study has been approved by St James ’ Hospital/AMNCH Research Ethics Committee and by the St Vincent 's Healthcare Group Ethics and Medical Research Committee . The results will be presented at international conferences and published in a peer review journal . Trial registration number NCT02310945 Recent evidence suggests that surgical trauma induces a process of central nervous system sensitisation that contributes to and enhances postoperative pain . These changes are also thought to be the underlying cause of much chronic pain . Central sensitisation is generated not only during surgery , but also postoperatively as a result of the inflammatory response to the damaged tissue . This knowledge provides a rational basis for pro-active , pre-emptive and postoperative analgesic strategies to reduce the neuronal barrage associated with tissue damage . Reduction or elimination of postoperative pain is therefore possible . We advocate the use of continuous extrapleural intercostal nerve block for postoperative analgesia in patients undergoing thoracotomy .  When this is begun pre-emptively ( by precutaneous , pre-incisional paravertebral block ) it is combined with an opiate and a non-steroidal anti-inflammatory drug premedication . In a r and omised study of 56 patients , pain scores of less than 0.5 cm on a 10 cm scale were produced , postoperative lung function was preserved and glucose and cortisol responses were significantly unchanged from preoperative values . Evidence that effective perioperative analgesia reduces the incidence of chronic post-thoracotomy chest wall pain was found in a retrospective study of 1000 consecutive thoracotomies . The endpoints of a zero pain score , complete preservation of preoperative lung function and prevention of the stress response to trauma are currently achievable and should be provided for virtually all patients undergoing chest surgery . Pre-empting pain must be the goal for all those involved in the postoperative care of patients Abstract Rheumatoid arthritis ( RA ) is characterised by pain and tenderness not only over inflamed or damaged joints , but also over apparently normal tissues . Experimental models suggest that these features result from changes of sensitivity within both peripheral and central neurones , but direct evidence from human disease is lacking . At present , most clinical studies have evaluated overall pain experience rather than activity within components of the nociceptive pathway . Therefore , the aim of this study was to assess the use of a capsaicin‐based technique to quantify changes of neuronal sensitivity in patients with RA . First 20 & mgr;l of capsaicin in solution ( 0.03 mg/ml ) was applied topically for 30 min to apparently normal skin on the forearm of control subjects and patients with RA . The subsequent development of mechanical hyperalgesia to pinprick stimuli was then measured at various time points using a 74.4‐mN von Frey hair . The relationship between the area of hyperalgesia and a number of clinical measures was determined .  Capsaicin‐induced mechanical hyperalgesia was found to decline with age in normal subjects ( r=0.47 , P<0.01 ) . The development of hyperalgesia had a similar time course in normal subjects and patients with RA .  The maximum area of hyperalgesia , however , was substantially larger in 35 RA patients ; 254.3±20.7 cm2 , compared with 35 normal controls ; 109±7.5 cm2 ( P<0.001 ) . An association was apparent between hyperalgesic area and a composite score of joint tenderness ( r=0.47 , P<0.01 ) , but not with overall pain score or a systemic marker of inflammation . These results provide evidence for enhanced sensitisation of a population of sensory fibres in RA . Peripheral sensory activity over the forearms of rheumatoid patients has previously been shown to be normal and the results suggest the presence of enhanced central mechanisms in this disorder . The correlation between  capsaicin‐induced hyperalgesia and joint tenderness in the RA patients implies that joint symptoms arise partially as a result of central , and not exclusively peripheral , factors . The study supports the use of capsaicin‐based techniques to explore nociceptive mechanisms in clinical disorders characterised by chronic pain & NA ; Persistent pain has been reported in up to 80 % of patients after limb amputation . The mechanisms are not fully understood , but nerve injury during amputation is important , with evidence for the crucial involvement of the spinal N‐methyl d‐aspartate ( NMDA ) receptor in central changes . The study objective was to assess the effect of pre‐emptively modulating sensory input with epidural ketamine ( an NMDA antagonist ) on post‐amputation pain and sensory processing . The study recruited 53 patients undergoing lower limb amputation who received a combined intrathecal/epidural anaesthetic for surgery followed by a r and omised epidural infusion ( Group K received racemic ketamine and bupivacaine ; Group S received saline and bupivacaine ) . Neither general anaesthesia nor opioids were used during the peri‐operative period . Pain characteristics were assessed for 12 months . The primary endpoint was incidence and severity of post‐amputation pain . Persistent pain at one year was much less in both groups than in comparable studies , with no significant difference between groups ( Group K = 21 % ( 3/14 ) and 50 % ( 7/14 ) ; and Group S = 33 % ( 5/15 ) and 40 % ( 6/15 ) for stump and phantom pain , respectively ) . Post‐operative analgesia was significantly better in Group K , with reduced stump sensitivity . The intrathecal/epidural technique used , with peri‐operative sensory attenuation , may have reduced ongoing sensitisation , reducing the overall incidence of persistent pain . The improved short‐term analgesia and reduced mechanical sensitivity in Group K may reflect acute effects of ketamine on central sensitisation . Longer term effects on mood were detected in Group K that requires further study In the present study , we examined clinical and laser-evoked potentials ( LEP ) features in two groups of chronic tension-type headache ( CTTH ) patients treated with two different approaches : intra-oral appliance of prosthesis , aim ing to reduce muscular tenderness , and 10 mg daily amitriptyline . Eighteen patients suffering from CTTH ( IHS , 2004 ) participated in the study . We performed a basal evaluation of clinical features and LEPs in all patients ( T0 ) vs. 12 age- and sex-matched controls ; successively , patients were r and omly assigned to a two-month treatment by amitriptyline or intra-oral device appliance . The later LEPs , especially the P2 component , were significantly increased in amplitude in the CTTH group . Both the intra-oral prosthesis and amitriptyline significantly reduced headache frequency . Total Tenderness Score was significantly reduced in the group treated by the prosthesis . The amplitude of P2 response elicited by stimulation of pericranial zones showed a reduction after amitriptyline treatment . The results of this study may confirm that pericranial tenderness is primarily a phenomenon initiating a self-perpetuating circuit , favoured by central sensitisation at the level of the cortical nociceptive areas devoted to the attentive and emotive compounds of pain . Both the interventions at the peripheral and central levels may interrupt this reverberating circuit , improving the outcome of headache BACKGROUND GPs are often the first point of contact for patients with prodromal schizophrenia . Early intervention , and therefore early detection , of schizophrenia is pivotal for the further disease course . However , recent studies have revealed that , due to its low prevalence in general practice and its insidious features , prodromal schizophrenia often remains unnoticed . AIM To test whether a repeated sensitisation method using clinical vignettes can improve diagnostic knowledge of GPs . DESIGN OF STUDY Postal survey using anonymous question naires . Repeated sensitisation model using clinical vignettes . SETTING GPs in three distinct regions in Switzerl and covering a general population of 1.43 million . METHOD The study was conducted between September 2008 and October 2009 . Question naires were sent to 1138 GPs at baseline , and at 6 and 12 months . After r and omisation , 591 GPs were sensitised at 1 , 3 , and 5 months , while no sensitisation was carried out in the remaining 547 GPs . RESULTS The overall response rate was 66 % ( 750 GPs ) . Sensitised GPs demonstrated a highly significant increase in diagnostic knowledge at 6 and at 12 months when compared to their own baseline knowledge scores and also to non-sensitised GPs ( P<0.001 ) . In particular , awareness of insidious features , such as functional decline and social withdrawal as signs of prodromal schizophrenia , accounted for this effect . CONCLUSION Theoretical knowledge of prodromal schizophrenia among GPs can successfully be increased by repeated sensitisation models using clinical vignettes BACKGROUND Central sensitization plays an important role in the chronic pain experienced by osteoarthritis ( OA ) patients . In this prospect i ve observational study , we investigated the influence of the level of preoperative central ly mediated symptoms measured by the Central Sensitization Inventory ( CSI ) on pain intensity after total knee arthroplasty ( TKA ) for OA . METHODS Ninety-eight female OA patients undergoing TKA were enrolled in this study . We assessed CSI scores , pain-related data , and other clinical data preoperatively . All patients received spinal anesthesia and postoperative epidural analgesia .  Pain intensity ( at rest and on movement ) and rescue meperidine requirements were assessed during postoperative days 1 and 2 . Also , pain intensity and patient satisfaction were assessed 1 month and 3 months after surgery . After the completion of all postoperative assessment s , we separated the study population into a preoperative CSI score ≥40 and < 40 group . We assessed pain-related data between the 2 groups at each assessment time . RESULTS Ninety-one patients completed the postoperative assessment s ( a preoperative CSI ≥40 group ; n = 44 , CSI < 40 group ; n = 47 ) . Patients with preoperative CSI ≥40 complained of a greater pain intensity ( P = 0.001 ) during postoperative days 1 and 2 and required a higher dose of meperidine rescue ( P = 0.003 ) than those with a preoperative CSI < 40 . The high CSI score group also showed a less favorable outcome in terms of pain relief on follow-up at 1 month ( P = 0.006 ) and 3 months ( P = 0.002 ) after surgery . In multivariate analysis , a preoperative CSI score ≥40 was the strongest determinant with 5.091 of the highest odds ratio ( 95 % CI 1.324 to 19.523 , P = 0.016 ) for predicting a persistent pain 3 months after surgery among demographic and pain-related variables . CONCLUSIONS OA patients with high levels of comorbid central ly mediated symptoms showed severe pain and increased analgesic requirements after TKA in the early postoperative period . Moreover , these patients seemed to be at higher risk of persistent pain , and a high CSI score was predictive of low patient satisfaction in terms of pain relief after surgery BACKGROUND pain is the leading symptom of osteoarthritis ( OA ) and is often chronic in nature , leading to significant morbidity and decreased quality of life . Duloxetine , a selective serotonin norepinephrine reuptake inhibitor has been demonstrated to have a central ly acting analgesic effect . OBJECTIVES the aim of the present study was to investigate the efficacy of duloxetine in reducing pain in older adults with knee OA . METHODS totally , 288 patients aged 65 years and above with primary knee OA were enrolled in this study . Patients were r and omised 1:1 . Totally , 144 received 60 mg/day of duloxetine HCL and 144 received placebo for 16 weeks . Outcome measures included pain reduction and improvement in physical functioning scores . Pain was assessed using the visual analogue pain scale ( VAS ; 0 - 100 mm ) . The Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) scores were used to assess function . RESULTS two-hundred and seventy four of the 288 patients completed the study . There was a statistically significant reduction in pain and a significant improvement in WOMAC scores at 16 weeks in the duloxetine group versus the placebo group . No serious side effects were reported . CONCLUSIONS the findings of the present study provide evidence for the efficacy and tolerability of duloxetine in reducing pain and subsequently improving function in older adults with knee OA . TRIAL REGISTRATION NCT01425827 Objective Erosive osteoarthritis is usually considered as an inflammatory subset of osteoarthritis ( OA ) . However , an inflammatory component is now recognised in all subsets of OA , so this subgroup of erosive or inflammatory OA is more difficult to conceptualise . The aim of this study was to compare routine CR and MRI to investigate erosion numbers and morphology to determine whether h and OA in general is a more erosive disease than previously recognised . Design and methods Fifteen patients with clinical ( OA ) of the small joints of the h and underwent MRI of one of the affected proximal interphalangeal ( PIP ) or distal interphalangeal ( DIP ) joints .  Conventional radiographs ( CR ) of the h and were also obtained . The MR images were review ed by two observers for the presence of central and marginal erosions . The site and morphology of any erosions was recorded . CR images of the same h and joint were scored independently for central and marginal erosions by the same observers . Results There was 100 % agreement between the observers for scoring erosions on CR . Agreement for the MRI scores was also excellent ( kappa = 0.84 ) . MRI detected 37 erosions , of which only 9 were seen on CR . The increase in sensitivity using MRI was much greater for marginal erosions ( 1 detected on CR , 19 on MRI ) than for central erosions ( 8 on CR , 18 on MRI ) . Using MRI 80 % of joints examined showed 1 or more erosions compared with 40 % using CR . If only marginal erosions were considered 80 % of joints were still considered erosive by MRI criteria , but only 1 showed evidence of erosion on CR . Morphologically central erosions appeared to represent areas of subchondral collapse and pressure atrophy . In contrast , marginal erosions resembled those seen in inflammatory arthritides . Conclusion Erosions , and particularly marginal erosions typical of those seen in inflammatory arthritis , are a more common feature of small joint OA than conventional radiographs have previously indicated OBJECTIVE Clinical tools are needed to identify and target a neuropathic-like phenotype , which may be associated with central sensitization ( CS ) , in osteoarthritis ( OA ) . The modified painDETECT question naire ( mPD-Q ) has face and content validity for identifying neuropathic-like symptoms in knee OA . To further vali date the mPD-Q , this study assessed the unknown relationship between mPD-Q scores and signs of CS on quantitative sensory testing ( QST ) in knee OA . DESIGN 36 Individuals were recruited with chronic , symptomatic , knee OA without other pain/neurological conditions . Reference QST data were obtained from 18 controls/32 eligible knees , enabling identification of sensory abnormalities/CS among case knees . A st and ardized question naire assessed psychological factors ( depressive symptoms and pain catastrophizing ) , and for individual knees , mPD-Q and pain intensity scores . A st and ardized/comprehensive QST protocol was conducted for each knee . QST signs of CS were defined as : mechanical hyperalgesia and /or enhanced temporal summation and /or allodynia . The relationship between the presence of CS ( yes/no ) and a pre-selected mPD-Q score ( ≤12 or > 12 ) , by knees , was assessed using generalized estimating equations . RESULTS Among 57 eligible case knees , 45.6 % had ≥1 sign of CS . Controlling for age , knees with higher mPD-Q scores ( > 12.0 ) had higher odds of having QST signs of CS ( adjusted odds ratio ( OR ) = 5.6 ; 95 % confidence interval ( CI ) , 1.3 - 22.9 ) . This relationship was unaffected by controlling for depression and pain intensity , but was attenuated by pain catastrophizing . CONCLUSIONS Among painful OA knees , higher mPD-Q scores were associated with greater odds of having signs of CS . Thus , the mPD-Q may aid the identification of CS in people with chronic knee OA Osteoarthritis ( OA ) is a common , chronic condition that affects most older adults . Adults with OA must deal with pain that leads to limited mobility and may lead to disability and difficulty maintaining independence . A longitudinal , r and omized clinical trial pilot study was conducted to determine whether Guided Imagery ( GI ) with Progressive Muscle Relaxation ( PMR ) would reduce pain and mobility difficulties of women with OA . Twenty-eight older women with OA were r and omly assigned to either the treatment or the control group . The treatment consisted of listening twice a day to a 10-to-15-minute audiotaped script that guided the women in GI with PMR . Repeated- measures ANOVA revealed a significant difference between the two groups in the amount of change in pain and mobility difficulties they experienced over 12 weeks . The treatment group reported a significant reduction in pain and mobility difficulties at week 12 compared to the control group . Members of the control group reported no differences in pain and non-significant increases in mobility difficulties . The results of this pilot study justify further investigation of the effectiveness of GI with PMR as a self-management intervention to reduce pain and mobility difficulties associated with OA Background Osteoarthritis ( OA ) is a common cause of pain and disability , and is the most common form of arthritis in the Western world . The most common joint to be affected is the knee . Pain and functional disability are common symptoms , which can lead to reduced quality of life and increase the risk of further morbidity . Current treatment aims to educate patients about the management of OA , reduce pain , improve function , decrease disability and reduce the progression of the disease . Education with clients has been described as a set of planned educational activities design ed to improve patients ' health behaviours and /or health status . The purpose of self‐education is to maintain or improve health , or , in some cases , to slow deterioration by increasing participant 's perception of self efficacy defined as an ability to control or manage various aspects of OA . To date , there is no systematic review of the literature undertaken to identify the effectiveness of self‐management educational activities for osteoarthritis of the knee . Objective The objective of this systematic review is to evaluate the effectiveness of  self‐management educational interventions on function and quality of life for adult subjects with OA of the knee . Search strategy A comprehensive search strategy was undertaken on data bases available from University of South Australia from their inception to January 2007 . Selection criteria R and omised controlled trials or clinical controlled trials were sought which evaluated any self management interventions for osteoarthritis knee . Critical appraisal of study quality was undertaken using Joanna Briggs Institute critical appraisal instruments . Data extraction was via the Joanna Briggs Institute st and ard data extraction form for evidence of effectiveness , and Review Manager Software was used to calculate comparative statistics . Results Thirteen trials were included in the review . Trials were clinical ly and method ologically heterogeneous . Pooled results indicate evidence of a beneficial effect from  self management strategies with reducing pain ( SMD ‐0.25 , 95%CI ‐0.36 to ‐0.13 , 11 trials 1379 participants ) . There was no effect on physical function ( SMD 0.13 , 95%CI ‐0.33 to ‐0.08 , eight trials , 1156 subjects ) . No beneficial effects were found from self management interventions with improving quality of life . We also found the exercise component of self management ( four trials ) demonstrated a benefit with reducing pain , improving function and quality of life . Exercise also offered a benefit over no exercise  . Overall method ological quality was moderate . Discussion Pooled results indicate evidence of a beneficial effect from self management strategies with reducing pain and improving function . Significant heterogeneity was found between trials . This was controlled for in the analysis but may be explained by heterogeneity in both the intervention and control group . The exercise component of self management programmes appears to contribute a significant benefit . Conclusion There is encouraging evidence of a small benefit from exercise in self management programs . Clear guidelines can not be provided for practice regarding the exercise content due to heterogeneity but overall benefit suggests this component should be emphasized and implemented in primary care self management programmes BACKGROUND The long-term use of opioid analgesic drugs to treat chronic non-cancer pain ( CNCP ) is a major component of pain pharmacotherapy . The interpretation of the evidence concerning its efficacy and risks is currently debated . METHODS An interdisciplinary evidence - and consensus-based S3 guideline was up date d on the basis of a systematic literature search ( CENTRAL , Medline , and Scopus data bases , from October 2008 to October 2013 ) ; meta-analyses of r and omized controlled trials ( ≥ 4 weeks ) ; and a consensus procedure , as specified by the AWMF regulations , including 22 medical and psychological societies and 2 patient self-help organizations . RESULTS 119 publications were used to up date the guideline , and 6 systematic review s with meta-analyses were performed . A nominal group process was used to formulate recommendations concerning the indications and contraindications for the treatment of CNCP with opioid analgesics and the manner in which such treatments should be carried out . Opioid analgesics are an option for the short-term treatment ( 4 - 12 weeks ) of chronic pain due to osteoarthritis ( pain intensity , st and ardized mean difference [ SMD ] : -0.22 and -0.26 ) , diabetic polyneuropathy ( SMD -0.74 ) , post-herpetic neuralgia ( SMD -0.58 ) , and chronic low back pain ( SMD : -0.29 and -0.74 ) . Long-term opioid treatment ( ≥ 26 weeks ) for these diseases benefits only about 25 % of patients . For other conditions , either short- or long-term treatment with opioid analgesics should be considered an individual therapeutic trial . Opioid treatment for pain is contraindicated by primary headaches and by any functional or mental disorder of which pain is a leading manifestation . CONCLUSION To minimize the risks of opioid analgesic treatment , physicians must be aware of its contraindications and must regularly reassess its efficacy and side effects . Pharmacotherapy should be combined with other types of treatment Objectives Few studies have addressed central sensitization symptoms and pain processing in childhood migraine . Our aims were to examine pain sensitivity and responses , including habituation , evoked by CO2 laser stimuli ( laser-evoked potentials ( LEPs ) ) in a cohort of children with migraine compared to non-migraine controls and to determine the correlation between LEP features and signs of central sensitization . Methods Thirty-five patients 8–15 years of age with migraines without aura were evaluated during the inter-critical phase and were compared to 17 controls .  LEPs were analyzed , and their main features were correlated with clinical symptoms including allodynia and pericranial tenderness . Results The laser-evoked pain threshold was lower and the N2P2 vertex complex amplitude was higher in children with migraines . Furthermore , habituation of vertex waves of LEPs clearly showed a tendency toward progressive amplitude enhancement in the migraine group . Acute allodynia and inter-critical pericranial tenderness correlated with trigeminal LEP features , particularly with the abnormal habituation pattern . Discussion Abnormalities of pain processing and symptoms of central sensitization appear to be characteristics of children with migraine . Reduced habituation and progressive amplification of cortical responses to laser stimuli indicate an overactive nociceptive system at the onset of migraine , and this hyperactivity may subtend allodynia and pericranial tenderness . Future prospect i ve trials may aid in the early identification of clinical phenotypes that display a tendency to develop into the chronic form of migraine , warranting a timely therapeutic approach BACKGROUND Refractory chronic cough causes substantial symptoms and quality -of-life impairment . Similarities between central reflex sensitisation in refractory chronic cough and neuropathic pain suggest that neuromodulators such as gabapentin might be effective for refractory chronic cough . We established the efficacy of gabapentin in patients with refractory chronic cough . METHODS This r and omised , double-blind , placebo-controlled trial was undertaken at an outpatient clinic in Australia . Adults with refractory chronic cough ( > 8 weeks ' duration ) without active respiratory disease or infection were r and omly assigned to receive gabapentin ( maximum tolerable daily dose of 1800 mg ) or matching placebo for 10 weeks . Block r and omisation was done with r and omisation generator software , stratified by sex . Patients and investigators were masked to assigned treatment . The primary endpoint was change in cough-specific quality of life ( Leicester cough question naire [ LCQ ] score ) from baseline to 8 weeks of treatment , analysed by intention to treat . This study is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12608000248369 . FINDINGS 62 patients were r and omly assigned to gabepentin ( n=32 ) or placebo ( n=30 ) and ten patients withdrew before the study end . Gabapentin significantly improved cough-specific quality of life compared with placebo ( between-group difference in LCQ score during treatment period 1·80 , 95 % CI 0·56 - 3·04 ; p=0·004 ; number needed to treat of 3·58 ) . Side-effects occurred in ten patients ( 31 % ) given gabapentin ( the most common being nausea and fatigue ) and three ( 10 % ) given placebo . INTERPRETATION The treatment of refractory chronic cough with gabapentin is both effective and well tolerated . These positive effects suggest that central reflex sensitisation is a relevant mechanism in refractory chronic cough . FUNDING National Health and Medical Research Council of Australia and Hunter Medical Research Institute , Newcastle , Australia Study Design Two-hundred-forty-three patients with chronic low back pain were studied in a prospect i ve comparative survey to determine whether the “ central ization phenomenon ” was associated with outcome after an interdisciplinary work-hardning program . Objective The hypothesis was that patients who demonstrated central ization during initial mechanical assessment would have better outcomes than non central izers . Summary of Background Data Overall subjects had decreased pain intensity ratings ( mean 10 % ) , increased lifting ability ( 6–8 kg ) , and a 59.2 % return-to-work rate at a mean of 9.7 months follow-up . Methods . Patients were classified as either central izers or non central izer  , based on results of their initial assessment , changes in pain ratings , one-time maximal weights lifted , Oswestry scores , and returen-to-work status were compared between groups . Results The central izers reported significant decreases in their maximum pain ratings ( central izers , 16 % non central izers , 6 % ) and had higher return-to-work rate ( central izers , 68 % ; non central izers , 52 % ) than the non central izers . Conclusion . Centrelization can help identify subgroups within the population with chronic low back pain and could be a useful goal setting and case management toll in the rehabilitation of low back pain Osteoarthritis ( OA ) is the most prevalent arthritis worldwide and is characterized by chronic pain and impaired physical function . We hypothesized that heightened pain in h and OA could be reduced with duloxetine or pregabalin . In this prospect i ve , r and omized clinical study , we recruited 65 participants , aged 40–75 years , with a Numerical Rating Scale ( NRS ) for pain of at least 5 . Participants were r and omized to one of the following three groups : duloxetine , pregabalin , and placebo . The primary endpoint was the NRS pain score , and the secondary endpoints included the Australian and Canadian H and Osteoarthritis Index ( AUSCAN ) pain , stiffness , and function scores and quantitative sensory testing by pain pressure algometry . After 13 weeks , compared to placebo , ANOVA found significant differences between the three groups ( P=0.0078 ) . In the intention-to-treat analysis , the pregabalin group showed improvement for NRS pain ( P=0.023 ) , AUSCAN pain ( P=0.008 ) , and AUSCAN function ( P=0.009 ) , but no difference between duloxetine and placebo ( P>0.05 ) was observed . In the per protocol analysis , NRS pain was reduced for pregabalin ( P<0.0001 ) and duloxetine ( P=0.029 ) compared to placebo . We conclude that central ly acting analgesics improve pain outcomes in people with h and arthritis , offering new treatment paradigms for OA pain Patients suffering from hip osteoarthritis ( OA ) are frequently symptomatic , and the disease can result in significant limitation of patients ’ activity and high social costs . Hip OA is generally managed with systemic treatments such as nonsteroidal anti-inflammatory drugs ( NSAIDs ) and /or symptomatic slow acting drugs . Viscosupplementation with hyaluronan ( HA ) or its derivatives , which aims to restore the physiological and rheological features of the synovial fluid to improve symptoms , is now a routinely prescribed treatment for OA of the knee . However , few data exist in the literature regarding the use of viscosupplementation in the treatment of hip OA . The objective of this prospect i ve , open , uncontrolled pilot study was to investigate the safety and effectiveness of intra-articular injection , under ultrasound control , of hylan G-F 20 for the treatment of OA of the hip . Twelve patients ( ≥40 years old ) with symptomatic hip OA were treated with one injection of 2 ml of hylan G-F 20 under ultrasound guidance . During the study , patients were evaluated for safety and efficacy using the Lequesne index , a visual analogue scale ( VAS ) measure of hip OA pain and analysis of NSAID consumption . Patients treated with hylan G-F 20 in this study showed clinical ly significant reductions in Lequesne and VAS scores and in the consumption of NSAIDs up to 3 months after the injection . In the 12 patients treated ( total of 14 injections ) , no systemic adverse events were observed . Three patients reported mild , local pain post-injection . This study demonstrates the potential of ultrasound-guided intra-articular injections of a viscosupplement into the hip joint and gives positive preliminary information about the safety and efficacy of hylan G-F 20 for the treatment of symptomatic hip OA CONTEXT GW406381 is an investigational , highly selective cyclooxygenase-2 ( COX-2 ) inhibitor that is effective in animal models of central sensitization and of inflammatory pain . OBJECTIVE To examine dose response for efficacy and safety of GW406381 in adults with osteoarthritis ( OA ) of the knee . DESIGN Two r and omized , double-blind , placebo- and positive-control studies : Study A , a 6-week nonflare design ; Study B , a 12-week flare design . PATIENTS 649 patients entered Study A ; 1331 patients entered Study B. INTERVENTIONS STUDY A GW406381 10 , 20 , 35 , or 50 mg , celecoxib 200 mg , or placebo . Study B : GW406381 1 , 5 , 10 , 25 , or 50 mg , celecoxib 200 mg , or placebo . MAIN OUTCOME MEASURES Study A , co- primary endpoints were change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain subscore and WOMAC question 1 . Study B co- primary endpoints were change from baseline in WOMAC pain and function subscores and Patient Global Assessment of Arthritis Condition . A closed hierarchical test procedure was prespecified . RESULTS Study A demonstrated that GW406381 50 mg was superior to placebo on WOMAC pain subscore ( mean difference from placebo -6.9 mm ; P= .012 ) . No clear dose response was observed , and the results with celecoxib were no different from those of placebo . In Study B , no dose of GW406381 was superior to placebo on the co- primary endpoints . Celecoxib was superior to placebo on all co- primary endpoints . Dose-related blood pressure and renovascular effects were seen with GW406381 . CONCLUSIONS Overall , clinical ly meaningful efficacy in pain related to OA of the knee was not demonstrated for GW406381 despite its peripheral and central sites of action & NA ; Inhibitory and facilitatory descending pathways , originating at higher central nervous system sites , modulate activity of dorsal horn nociceptive neurons , and thereby influence pain perception . Dysfunction of inhibitory pain pathways or a shift in the balance between pain facilitation and pain inhibition has been associated with the development of chronic pain . The N‐methyl‐d‐aspartate receptor antagonist ketamine has a prolonged analgesic effect in chronic pain patients . This effect is due to desensitization of sensitized N‐methyl‐d‐aspartate receptors . Additionally , ketamine may modulate or enhance endogenous inhibitory control of pain perception . Diffuse noxious inhibitory control ( DNIC ) and offset analgesia ( OA ) are 2 mechanisms involved in descending inhibition . The present study investigates the effect of a ketamine infusion on subsequent DNIC and OA responses to determine whether ketamine has an influence on descending pain control . Ten healthy subjects ( 4 men/6 women ) received a 1‐hour placebo or S(+)‐ketamine ( 40 mg per 70 kg ) infusion on 2 separate occasions in r and om order . Upon the termination of the infusion , DNIC and OA responses were obtained . After placebo treatment , significant descending inhibition of pain responses was present for DNIC and OA . In contrast , after ketamine infusion , no DNIC was observed , but rather a significant facilitatory pain response ( P < 0.01 ) ; the OA response remained unchanged . These findings suggest that the balance between pain inhibition and pain facilitation was shifted by ketamine towards pain facilitation . The absence of an effect of ketamine on OA indicates differences in the mechanisms and neurotransmitter influences between OA and DNIC . Diffuse noxious inhibitory control responses following a 1‐hour low‐dose ketamine treatment displayed facilitation of pain in response to experimental noxious thermal stimulation Depression is significant among patients with arthritis and musculoskeletal illnesses . However , the impact of depression on osteoarthritis has not been extensively studied . This article highlights the close links between these 2 prevalent chronic conditions , and the associated individual and societal burden . Results from a large clinical trial of depressed older patients with arthritis showed that a focused , collaborative depression care intervention not only decreased depression but also improved arthritis-associated outcomes , such as pain severity and arthritis-related limitations in daily activities . Relative to patients given usual care , patients receiving intervention also reported better health status and higher quality of life . Analyses of the depression interventions uncovered a reciprocal interrelation between depression and pain . Higher severity of either depression or pain decreased the benefits of systematic depression treatment and was associated with worse pain and depression outcomes . Current approaches to management of depression and arthritis do not reflect readily-available evidence -based treatment . A pilot study using a combined approach to address both depression and pain problems among elderly patients with depression and osteoarthritis suggested that benefits for depression , pain , and functional outcomes are strengthened by providing both  pain and depression care management . An integrated depression and pain program using evidence d-based pharmacologic and nonpharmacologic treatments is needed to achieve optimal depression and pain outcomes . Currently , a r and omized trial is under way to evaluate effectiveness of a combined pain and depression intervention using pharmacologic and nonpharmacologic therapies . Key intervention components in these 2 innovative and integrated depression and pain programs can guide clinicians to treat both depression and pain with more focus and intensity BACKGROUND Recommendations state that acetaminophen should be used in preference to nonsteroidal anti-inflammatory drugs in the initial treatment of symptomatic osteoarthritis ( OA ) of the hip or knee , because of lesser toxicity and the pervasive belief that acetaminophen is not only effective in treating OA pain but is of equal analgesic efficacy as nonsteroidal anti-inflammatory drugs . METHODS This was a r and omized , double-blind , placebo-controlled trial of diclofenac sodium , 75 mg twice daily , vs acetaminophen , 1000 mg 4 times daily , in 82 subjects with symptomatic OA of the medial knee . Osteoarthritis was quantitated radiographically , and subjects met stringent baseline pain criteria . The primary evaluation of efficacy used the Western Ontario and McMaster Universities Osteoarthritis Index , with evaluations at screening , baseline , and 2 and 12 weeks after treatment . Intention-to-treat analysis was used . RESULTS Twenty-five subjects were r and omized to diclofenac , 29 to acetaminophen , and 28 to placebo . The groups were closely matched for age , sex , body mass index , prior use of OA medications , baseline pain , and radiographic features . At 2 and 12 weeks , clinical ly and statistically significant ( P<.001 ) improvements were seen in the diclofenac-treated group ; however , no significant improvements were seen in the acetaminophen-treated group ( P = .92 at 2 weeks and .19 at 12 weeks ) . Stratification of subjects according to baseline pain , pre study OA medication , and radiographic grade showed no clear pattern of preferential response to diclofenac , and did not reveal a subset of subjects who responded to acetaminophen . CONCLUSIONS Diclofenac is effective in the symptomatic treatment of OA of the knee , but acetaminophen is not . A review of the literature reveals that there is scanty published evidence for a therapeutic effect of acetaminophen relative to placebo in patients with OA of the knee , because most published studies use active comparators ( ie , nonsteroidal anti-inflammatory drugs ) only . The advocacy of acetaminophen use in subjects with OA of the knee should be reconsidered pending further placebo-controlled studies & NA ; Few studies have directly compared the clinical features of neuropathic and non‐neuropathic pains . For this purpose , the French Neuropathic Pain Group developed a clinician‐administered question naire named DN4 consisting of both sensory descriptors and signs related to bedside sensory examination . This question naire was used in a prospect i ve study of 160 patients presenting with pain associated with a definite neurological or somatic lesion . The most common aetiologies of nervous lesions ( n=89 ) were traumatic nerve injury , post herpetic neuralgia and post stroke pain . Non‐neurological lesions ( n=71 ) were represented by osteoarthritis , inflammatory arthropathies and mechanical low back pain . Each patient was seen independently by two experts in order to confirm the diagnosis of neuropathic or non‐neuropathic pain . The prevalence of pain descriptors and sensory dysfunctions were systematic ally compared in the two groups of patients . The analysis of the psychometric properties of the DN4 question naire included : face validity , inter‐rater reliability , factor analysis and logistic regression to identify the discriminant properties of items or combinations of items for the diagnosis of neuropathic pain . We found that a relatively small number of items are sufficient to discriminate neuropathic pain . The 10‐item question naire developed in the present study constitutes a new diagnostic instrument , which might be helpful both in clinical research and daily practice
Results There is good evidence for a role of central sensitisation in chronic OA pain in a subgroup of patients .
Biomarkers may be helpful for confirming the presence of central sensitisation , especially when there is diagnostic uncertainty .
Several non‐pharmacological and pharmacological treatments may be effective in OA patients with central sensitisation features .
Multimodal therapy may be required to achieve control of symptoms .
Summary Aims The aim of this non‐ systematic review was to provide a practical guide for clinicians on the evidence for central sensitisation in chronic osteoarthritis ( OA ) pain and how this pain mechanism can be addressed in terms of clinical diagnosis , investigation and treatment .
Clinical ly , a central sensitisation component in chronic OA pain can be suspected based on characteristic pain features and non‐pain features seen in other conditions involving central sensitisation .