bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intraplantar zymosan as a reliable, quantifiable model of thermal and mechanical hyperalgesia in the rat
Authors: Meller S.T. , Gebhart G.F. 
Published: February 2004

The study of the mechanisms of thermal and mechanical hyperalgesia produced in human inflammatory conditions is dependent on a reliable, consistent model. The present investigation shows that the intraplantar administration of zymosan in the rat hindpaw produces a reliable and quantifiable thermal and mechanical hyperalgesia accompanied by oedema that closely mimics the symptoms of inflammation in man.Prior to the intraplantar injection of zymosan, there was no significant difference in withdrawal latencies, mechanical withdrawal thresholds or paw thickness between the left and right hindpaws. The intraplantar injection of zymosan (0.313–6.25 mg), an extract from yeast, produced a dose‐ and time‐dependent thermal and mechanical hyperalgesia, a robust oedema and, at the greatest doses, produced evidence of spontaneous pain. At the least dose of zymosan tested (0.313 mg), there was a slight oedema; oedema was greatest at dosages 2.5 mg and was always maximal by 30 min postinjection, irrespective of the dose. On the other hand, thermal and mechanical hyperalgesia showed a more complex dose‐ and time‐dependence. Mechanical hyperalgesia did not appear until dosages 1.25 mg and was maximal by 5 mg. In addition, mechanical hyperalgesia showed a time‐dependent progressive onset so that hyperalgesia was maximal by the 4‐h testing time‐point. In contrast, thermal hyperalgesia showed a biphasic nature with two apparent maximal time‐points (30 min and 4 h). There was an early‐phase thermal hyperalgesia (maximal by 30 min) that was dose‐dependent at dosages 2.5 mg (not apparent at lower dosages) and a late‐phase (maximal by 4 h) that was dose‐dependent at dosages 0.0625 mg. At the greatest doses administered (5 and 6.25 mg), there was evidence of spontaneous pain from the time of injection for up to 4 h that was characterized by occasional spontaneous flicking of the hindpaw, but more usually by holding the paw in an elevated position for extended periods of time. In addition, at the greatest dose tested (6.25 mg), all rats showed evidence of licking, biting and shaking of the injected hindpaw for up to 30–45 min after injection.These data demonstrate that the intraplantar injection of zymosan is a reliable and quantifiable model of tonic pain characterized by a dose‐ and time‐dependent thermal and mechanical hyperalgesia accompanied by a robust oedema. This model is likely to be a useful, reliable model in which to study further the central and peripheral mechanisms of hyperalgesia.
Quantification of local and referred pain in humans induced by intramuscular electrical stimulation
Authors: Laursen R.J. , Graven‐Nielsen T. , Jensen T.S. , Arendt‐Nielsen L. 
Published: February 2004

The basic knowledge related to referred muscle pain is limited. To study referred pain, an experimental model using intramuscular electrical stimulation has been developed.Four experiments were performed: (1) the thresholds for eliciting local (LPT) and referred pain (RPT) were determined; (2) stimulus‐response functions relating stimulus intensity, pain intensity ratings and size of pain areas were determined; (3) inter‐ and intrasession variabilities were assessed; and (4) prolonged stimulations were given with a duration of 10 min to evaluate temporal aspects of the referred muscle pain.Intramuscular electrical stimulation of the tibialis anterior muscle elicited pain at the stimulation site in 94% of the subjects, and referred pain in 78% of the subjects. Referred pain was located in the anterior part of the ankle. The mean RPT was 72% higher than the mean LPT (p≤0.01). Correlation was found between stimulus intensity, sensory/pain rating scores and size of pain areas (0.74≤r≤0.98, p<0.04). Size of pain areas and sensation/pain rating scores were correlated (0.86≤r≤0.97, p<0.01). Intersession variability showed that the LPTs were not significantly different (p>0.16), but the RPTs were disparate (p<0.02). Intrasession values revealed a significant difference between the five LPTs, RPTs, local and referred pain rating scores. The size of the local and referred pain areas remained constant. Prolonged stimulation at 150% of RPT showed that the onset (the first occurrence of pain) of referred pain occurred significantly later (43 s ± 80 s) than at the local pain site (p<0.03).This study showed that local and referred muscle pain can be elicited by intramuscular electrical stimulation, and indicated that temporal and spatial summation may be involved in the elicitation of referred muscle pain.
Cutaneous norepinephrine application in complex regional pain syndrome
Authors: Birklein F. , Riedl B. , Claus D. , Neundörfer B. , Handwerker H.O. 
Published: February 2004

Patients with complex regional pain syndrome (CRPS) (n=20) were examined in order to evaluate cutaneous reactions to norepinephrine (NE) on both the affected and the unaffected limb in comparison to healthy controls. Sixteen female and four male patients suffering from very acute and therefore untreated CRPS with a mean duration of 5.5 weeks were included in this study. Two groups of healthy volunteers served as control groups: the first group (n =18) according to the same study protocol as CRPS patients, and the second group (n =10) after warming up one limb. Norepinephrine was iontophoresized (0.2 mA, 120 s) and vasoconstriction was recorded by laser‐doppler flowmetry. Pain sensations were simultaneously rated on a visual analogue scale (VAS). Five patients underwent a second trial with higher intracutaneous NE concentrations in order to study possible dose‐dependent effects of NE on pain sensation. After acclimatization, skin temperature was recorded by infra‐red thermography.The NE‐induced reduction of skin blood flow was significantly higher in the affected limb in the patient group (33.0 vs 11.2%, p<0.005). None of the patients reported pain or hyperalgesia. The skin temperature of CRPS patients was significantly higher in the affected limb (34.7 vs 32.5°C, p<0.001). The first control group did not show any difference between left and right sides concerning NE‐induced vasoconstriction or skin temperature. The second control group had an increased unilateral skin temperature after warming up (35.0 vs 34.3°C, p<0.006) and demonstrated a significantly increased vasoconstriction on the warmer side (52.0 vs 20.2%, p<0.03) corresponding to findings in patients with acute CRPS.The present study proves that there are signs of decreased sympathetic activity in the affected limb in very acute CRPS. However, no indication was found for increased sensitivity of vascular α‐receptors in the very acute stages of CRPS, and there was also no indication for a significant direct contribution of the sympathetic nervous system to pain in very acute CRPS.
The pharmacokinetics of lignocaine in humans during a computer‐controlled infusion
Authors: Dyck J.B. , Wallace M.S. , Lu J.Q. , Rossi S.S. , Yaksh T.L. 
Published: February 2004

Several types of chronic pain syndromes are effectively treated with sodium channel blockers such as lignocaine. Further investigation of this therapeutic modality would be facilitated by refinement of the parameters describing lignocaine distribution and elimination. This would allow precise lignocaine infusion by a computer‐controlled infusion to attain and maintain stable target lignocaine concentrations.Arterial blood samples were obtained at frequent intervals during a computer‐controlled infusion of lignocaine in 12 adult human volunteers. Plasma lignocaine concentrations of 1, 2, 3, 4 and 5μg/ml were targeted for 15 min at each concentration. A three‐compartment mammillary pharmacokinetic model best described the resulting concentration vs time profile. A population pharmacokinetic analysis was performed using three different techniques; the two‐stage, pooled and mixed effects modelling.There was marked overshoot of the plasma concentration above the target prior to refinement of the pharmacokinetic parameters. The best parameters of a three‐compartment mammillary model fit to the measured concentration using the pooled data approach were: V1 = 7.44, V2 =11.5 and V3 = 97.71; Cl1 = 0.585, Cl2 = 2.23 and Cl3 =1.64 Umin. Similarly calculated parameters using NONMEM were V1 = 6.99, V2 =12.2 and V3 =1341; Cl1 = 0.703, Cl2 =1.24 and Cl3 =1.49 Umin. The addition of age as a covariate of the pharmacokinetic parameters improved the model in both cases. Height, lean body mass and body surface area as covariates of the pharmacokinetic parameters did not improve the predicted value of the model. Prospective testing of the pharmacokinetic parameters will be required to define whether they function well.The refinement of pharmacokinetic parameters for the computer‐controlled intravenous infusion of lignocaine will facilitate further research in pain therapy. Published lignocaine pharmacokinetic values have a relatively large central volume of distribution, and hence, when implemented as a computer‐controlled infusion, result in dramatic overshoot shortly after targeting a higher plasma concentration. In light of the long‐lasting pain relief provided by sodium channel blockade in neuropathic pain states, overshoot of plasma concentrations must be avoided if the concentration vs effect relationship is to be defined.
Increased non‐articular tenderness in patients on steroid therapy
Authors: Buskila Dan , Schleifer Elena , Odes H. Selvyn , Neumann Lily 
Published: February 2004

Increased non‐articular tenderness and tender shins have been suggested to be associated with steroid therapy in patients with lupus. The aim of the present study was to extend this observation in a different disease, inflammatory bowel disease (IBD), and to examine the relationship between tenderness, dosage and duration of steroid therapy.Eighty‐seven patients with 11313, 23 of them on steroid therapy, were assessed for disease activity and nonarticular tenderness. A count of 18 tender points was conducted by thumb palpation, and tenderness thresholds were assessed by dolorimetry at four shin sites, nine tender point sites and four control point sites. Patients on steroids were significantly more tender than subjects not on steroids: their mean tender point counts were 13.3 and 6.7 (p<0.001), respectively, and the dolorimetry thresholds at all three sites were significantly lower in the steroid group (p<0.001). Increased tenderness was also associated with increased steroid dosage. However, tenderness was not related to duration of steroid therapy, to gender, or to previous steroid therapy being discontinued at least a year ago. Disease activity was neither related to tenderness nor to steroid treatment.The demonstration of increased tenderness in IBD patients on steroid therapy, in addition to earlier observations in lupus, may suggest that such a relationship is not disease specific. The recognition of this association is important to physicians treating patients with steroids and will prevent misinterpretations of complaints about tender shins and diffuse tenderness as part of the disease entity itself.
Different direct pathways of locus coeruleus to medial prefrontal cortex and centrolateral thalamic nucleus: Electrical stimulation effects on the evoked responses to nociceptive peripheral stimulation
Authors: Condés‐Lara M. 
Published: February 2004

Projections from the locus coeruleus (LC) to the centrolateral thalamus (C1) and the medial prefrontal cortex (PfCx) were studied using orthodromic and antidromic stimulation techniques. The LC is a major noradrenergic source in the central nervous system, and its descending projections provide an important source of pain suppression at spinal level. Previously, the author has described a cortico‐thalamic loop involved in pain modulation. The present paper reports on a study of the participation of LC as part of an ascending pain‐control system acting on the cortico‐thalamic loop.Rats were anaesthetized with halothane, and single unit recordings were made in LC using glass micropipettes. Stainless steel electrodes were placed in cortex and thalamus for electrical stimulation.Stimulation in PfCx or C1 produces antidromic responses in neurons in LC. The latencies, conduction velocity and location of neurons in LC projecting to PfCx or Cl structures are described. Separate projections to both structures have significantly different conducting velocities, arriving earlier at Cl (mean conduction velocities 0.27 and standard deviation ±0.06m/s) and then at PfCx (mean conduction velocities 0.20± 0.04 m/s). The presence of orthodromic responses suggests reciprocal connections. The paper also describes the suppression of spontaneous and nociceptive‐evoked activity in the PfCx and Cl following electrical stimulation in LC.It is proposed that the LC innervation could be associated with an ascending noradrenergic system acting upon a C1‐PfCx pain‐modulation mechanism.
Systemic morphine in the prevention of allodynia in the rat spinal nerve ligation model of neuropathic pain
Authors: Kontinen V.K. , Paananen S. , Kalso E. 
Published: February 2004

Peripheral nerve injury may lead to neuropathic pain that has been considered unresponsive to opioids. In animal models of neuropathic pain, there are previous data of both increased and decreased effect of opioids, but only limited information of the long‐term effects of opioid treatment on the development of the symptoms of neuropathy. The possibility of preventing the development of signs of neuropathy with either a single preinjury injection or chronic postinjury administration of morphine was studied in rats with unilateral peripheral neuropathy due to tight ligation of the L5 and L6 spinal nerves.These rats developed both mechanical and cold allodynia, but no thermal hyperalgesia. Neither subcutaneous morphine given as single injection (10 mg/kg) before the nerve injury nor chronic administration starting immediately after surgery using slow‐release pellets (one, two or five pellets containing 75 mg of morphine, resulting in a total dose of 75, 150 or 375 mg) prevented the development of either mechanical or cold allodynia. No autotomy, signs of distress, altered social behaviour or morphine withdrawal was seen in any of the rats. The fact that neuropathic painlike symptoms were not attenuated by any of the treatments studied could indicate that neither premedication nor postoperative pain management with systemic morphine is effective in preventing postoperative neuropathic pain.
Long‐term intrathecal (i.t.) infusion of bupivacaine relieved intractable pain and spasticity in a patient with multiple sclerosis
Authors: Dahm P.O. , Nitescu P.V. , Appelgren L.K. , Curelaru I. 
Published: February 2004

There is no reliable method to relieve both ‘refractory'; pain and spasticity in patients with multiple sclerosis (MS). This paper reports on the long‐term use of continuous intrathecal bupivacaine infusion in such a patient.The patient under study was a 56‐year‐old woman affected for 18 years by MS, unsuccessfully treated with analgesics, baclofen, opioids, peripheral neurolysis (obturator nerves, lumbar plexus) and six intrathecal neurolyses of the L4‐S3 nerve roots, each time with 1.5 ml of 50% phenol in glycerol. Intrathecal baclofen was not considered (MS with bulbar location and neurogenic pains). An intrathecal catheter was inserted via the L3‐L4 interspace and its tip was placed at the height of the T12‐L1 intervertebral disc. An intrathecal infusion of 0.5% bupivacaine at a rate of 3 ml (=15 mg)/day was started.The infusion rate was gradually increased from 20 mg on the first day to 95 mg/day after 68 days. The pain intensity decreased from a mean visual analogue score (VAS/mean) of 7 before treatment to 1 (on a 0–10 scale) during the intrathecal treatment. The patient became free from pain and spasticity. No side‐effects or complications were recorded. The treatment was given for 712 days, at which point the patient died (unrelated to the treatment).Intrathecal infusion of bupivacaine relieved ‘refractory'; spasticity and pain in a MS patient in whom administration of intrathecal baclofen was contraindicated and neurodestructive procedures had been inefficient.
Assessing surgical patients' expectations and subsequent perceptions of pain in the context of exploring the effects of preparatory information: raising issues of gender and status
Authors: Campbell Carol , Guy Alison , Banim Maura 
Published: February 2004

The present study explored both patients' expectations and experiences of pain in the context of utilizing an established research procedure, which previously reported a significant effect of instructional information on post‐surgical recovery. No research to date has systematically attempted to identify pre‐operative expectations of post‐operative pain, nor has it compared pre‐ and post‐operative ratings. A further variable scrutinized during the study was patient gender.Thirty‐two males and 31 females undergoing two types of elective surgery were randomly allocated into experimental and control conditions by a third party. Patients in the experimental group received additional instruction information pre‐operatively from the anaesthetist and the control group received the routine preoperative visit. Using a numerical pain scale, all participants provided ratings of expected pain levels and subsequently rated their pain following surgery.Results obtained were contrary to expectations with respect to the effects observed by the established study as instructional information had no significant effect on recovery variables. However, the study did suggest that pre‐ and post‐operative pain ratings were broadly equivalent. A significant gender difference was also found with male patients expecting less pain than they perceived and an opposite pattern for females. Measuring both pain expectations and perceptions is considered a useful technique to inform pain management and is worthy of further investigation. The inconsistent effect of instructional information and the gendered rating patterns are considered in relation to gender and status differentials between health providers and have important implications for future research.
Pain and inflammatory hyperalgesia induced by intradermal injections of human platelets and leukocytes
Authors: Blunk J. , Osiander G. , Nischik M. , Schmelz M. 
Published: February 2004

Acute and prolonged inflammatory processes, induced by intradermal injections of autologous platelet preparations, leukocytes, platelet‐leukocyte mixtures and vehicle solutions, were monitored in 20 human subjects for up to 48 h. Psychophysical methods were employed to assess the time course of pain response, and the development of hyperalgesia. Time course of the axon reflex erythema was analysed by computer based videography. Injections of functionally intact platelets [4.4 × 107 ± 0.6 × 107 in 50 μl (mean ± SEM)] caused distinct pain sensations [median pain rating 7.25 (25–75%: 6.5–7.5) on a scale form 0–10]. Both platelets injected through a microfilter (0.2 gm) and heat‐inactivated platelets induced similar initial pain response; however, pain duration was significantly shorter than for intact platelets. Control injections of leukocytes (5.4 × 106 ± 3.7 × 106 in 50 μl) and of vehicle solutions only caused minute pain sensations.Although platelet concentration in the mixture was only 50%, platelet/leukocyte mixtures produced axon reflex erythema that were significantly larger than those seen with naive platelets alone (11.1 ± 2.3 vs 8.3 ± 0.8 cm2), Intact platelets and heat‐inactivated platelets both induced mechanical hyperalgesia and skin indurations at the injection site. Both reactions peaked between 6 and 24 h after the injection and disappeared within 48 h. Neither hyperalgesia, nor the development of indurations was noted at the injection sites of filtered platelets and vehicle solutions. Leukocyte injections induced hyperalgesia and indurations only in samples with a platelet contamination of more than 50 000 cells/μl. We conclude that platelets induce acute pain responses due to a soluble factor, whereas the development of hyperalgesia and the formation of indurations depends on a membrane‐bound factor. Moreover, platelets and leukocytes act synergistically in nociceptor activation.
A survey of postoperative pain treatment in children of 3–14 years
Authors: Baños Josep‐Eladi , Barajas Conchita , Martin Maria Luisa , Hansen Elisabet , de Cos Maria Angeles , Bosch Félix , Martin Rafael , Marco Joan , Dierssen Trinidad 
Published: February 2004

There is a lack of information concerning the characteristics of pediatric postoperative pain in Southern European countries. The aim of this study was to document how postoperative pain in children was managed routinely at Spanish surgical wards.The study was carried out in three hospitals on the first postoperative day. Children were divided in four groups according to their age (years): Group I (3–5), 11(6–8), III (9–11) and IV (12–14). The parameters evaluated were: analgesia characteristics (type of prescription, drug used and route of administration, prescribed dose and whether the drug was or was not administered, need of non‐prescribed analgesics) and the postoperative pain intensity. The results were analysed using descriptive statistics. U‐Mann Whitney, χ2 ANOVA, Kruskall‐Wallis and Student's t‐test were also used.A total of 348 children ranging from 3 to 14 years were studied. The average age (± SD) was 8.2 ± 3.3 and the majority were male (74%). Urologic surgery was the most frequent type of operation, with age (p <0.05) and hospital differences (p<0.001). The majority of the patients (52%) were prescribed an analgesic, but only 26% of them had an analgesia order at fixed dosage intervals. Differences among the hospitals were observed (p<0.001). The most commonly used analgesics were metamizol, propyphenazone, paracetamol and codeine. Differences in choice of drug in relation to age and hospital were significant (p < 0.001). Rectal was the preferred route of drug administration. Patient's age was unrelated with the prescribed analgesic dose. An average of 68% of prescriptions were given and half of the patients without scheduled analgesia needed to have analgesics administered. Around 20% of patients had high pain scores.Few paediatric patients are given analgesics at fixed dose intervals to treat postoperative pain. Pain relief therapy for children differs notably to that of adults, in respect to the drugs prescribed and the administered route.
Capillary blood sampling: relation between lancet diameter, lancing pain and blood volume
Authors: Fruhstorfer Heinrich , Schmelzeisen‐Redeker Gnöther , Weiss Thomas 
Published: February 2004

The relation between pain of capillary blood sampling and lancet diameter was studied in 52 healthy subjects. The tips of six fingers were pricked with a Softclix® II lancing device using lancets with identical facet geometry but needle diameters of 0.3, 0.4 and 0.8 mm. Two penetration depths (0.9 and 1.2 mm) were applied. Pain intensity and blood volume were recorded.At a puncture depth of 0.9 mm, pain did not differ between the three lancets. Pain increased with penetration depth, and at 1.2 mm the thicker lancets were somewhat more painful than the thinner ones. Blood volumes increased with lancet diameter and penetration depth. If the pain for punctures providing just enough blood for a glucose test (≥10 μl) was compared, there was no difference between the lancets.It can be concluded that lancet diameter is of minor importance for the patient.