Complex Regional Pain Syndrome Type I : measurements and treatment

Field: Medicine (Health Sciences)

Immunological mechanismsMailis et al investigated the correlation of HLA class I and II expression in 15 patients with poor treatment outcome.Their study demonstrated elevated levels of both types III.A antigens in 80% of treatment resistant patients*-.Several investigators demonstrated an association with HLA-'' -''.High expression of heritable antigens has also been reported in murinc model of neuropathic pain-*.Despite the clinical symptoms, which resemble an inflammatory response, a humoral or cellular immune activation could never be proved.However, the coincidence of signs of inflammation with trophic changes and mechanical hyperalgesia in CRPS I strongly resembles neurogenic inflammation.Activation of primary aflerents leads to the release of calcitonin gene-related peptide (CCiRP) and substance P (SP) from nerve endings.Release of CGRP leads to an increase in peripheral blood flow (vasodilatation) by an action on the arterioles, whereas release of substance P, in addition, induces plasma protein extravasation from venules^-2*.27 in CRPS I Weber et al.^s were able to show that the excitability of primary aft'erents and thereby the release of neuropeptides is increased.In the acute stage this may explain increased skin temperature, edema and trophic changes (increased hair-and nail growth).It is assumed that neuropeptides are mainly released from the so-called sleeping' mechano-insensitive nociceptors.which are sensitised by the initial trauma and the resulting processes of regeneration.Recruitment of sleeping' nociceptors predominantly leads to mechanical hyperalgesia.another marked sign in CRPS I*.However, one has to bear in mind that neuropeptides are released not only in the periphery, but also from the central endings of the primary aflerents.After nerve trauma, the SP receptor (NKI-R) will be up-regulated in dorsal horn neurones of the spinal cord, and thereby SP will initiate sensitisalion of central pain transmission neurones, a distinctive mechanism leading to pain chronicity.Acutely after -3 -trauma, in inflammatory processes or triggered by ischemia and reperfusion.oxygen-derived free radicals are produced in the affected tissues.Animal models with intra-artenal infusion of tcrt-butylhydroperoxide, a free radical donor, strongly resemble clinical symptoms of acute CRPS I: edema, increased skin temperature, impaired function and pain behaviour'-*.f A'! Neuropathic mechanism ' v Increased skin temperature and increased sweating which are often seen in CRPS I patients arc caused by vasoconstrictor hypo-activity and sudomotor hyperactivity.According to Wanner el al^ this impaired sympathetic output function must be due to functional alterations of the central nervous system.Rommel ct al"' also support the central mechanisms.In their prospective study they reported sensory deficits extending beyond the painful area of the affected limb"*.They noted a significant increased frequency of mechanical allodynia and movement disorders in patients with hemisensory impairment or sensory deficits in the upper quadrant compared to those with impairment limited to the affected limb.Similar significant increase were also noted for motor impairment and correlated with allodynia/hyperalgesia.In conclusion they report that iunrlMVuJ J».I. UVJ»J.V, W. V A? iwtfr*' pratvw.vrgrrr^nY restnk rrr motor •sensory impairment in CRPS I patients.These assumptions are supported by ladarora et al." Positron Emission Tomography (PET) performed in patients with chronic posttraumatic neuropathic pain or neuralgia demonstrated a significant decreased level of thalamic activity contralateral to the symptomatic side compared to normal controls.INvcholojiical aspects The majority of patients with chronic pain, regardless of the cause and origin, experience some psychologic symptoms in the course of their illness^-.From a behavioural point of view, Fordyce and Vlaeyen described that, when pain becomes chronic, the relationship between organic pathology and pain experience becomes less direct'*-*•.In the biomedical model, nociception is controlled by somatic factors: a nociceptive stimulus is followed by a so-called respondent pain reaction.The value of the biomedical model becomes limited in the case of chronic pain.At this point, the relationship between a nociceptive stimuli and pain behaviour attenuates because an operant pain reaction has developed.The behaviour is not directly related with a nociceptive stimulus"-H -4 -in patients with CRPS I the behaviour is said to be unproportional to a known organic cause**.It is demonstrated that compared to patients with localised neuropathic pain and chronic back pain patients.CRPS I do not display an unique or unusual pattern in terms of their symptom reporting, anxiety symptoms, pain related dysfunction, illness beha\ iour.and psychological distress".However, other studies show that CRPS I patients display higher >-.•»•* emotional distress, i.e. somatisation and phobic anxiety, than non-CRPS I patients'*'"'.Although, the possibility of a psychopathological aetiology of CRPS I continues to receive support, it is still unclear whether CRPS I patients differ from non-CRPS I patients on u cognitive level.CLINICAL PRESENTATION Sensory symptoms Pain and hyperesthesia arc the predominant sensory symptoms.Hie pain is often described as aching, burning, pricking or shinning.It is localised deep in the tissue.Abnormal sensations to mechanical-and thermal stimuli or upon joint movement are frequently presented.Allodynia is often described.Sensory deficits are common in CRPS I patients'' *•• **• *'.Autonomic symptoms Autonomic signs include swelling, colour and temperature changes, and sweating abnormalities.The swelling is often aggravated by physical activities, painful stimuli, environmental and local temperature changes, and hydrostatic pressure'-2**.41.42 Motor-and dystrophic symptoms Muscle weakness, tremor, dystonia, myoclonus and decreased range of motion often accompany CRPS I. Range of motion is decreased by joint effusion early in the disease and by contraction and fibrosis later in the disease'-^.Decreased grip strength is observed in 78% of the patients'".Tremor has been reported in 24% to 60% of the patients'*-*'•**.Change in nail and hair growth in affected extremity is frequently reported in patients suffering of CRPS I.These symptoms are often accompanies with skin changes including fibrosis, hyperkeratosis and thin glossy skin''.Diagnostic criteria systems ~ ' Like other neuropathic pain syndromes the main symptom of CRPS I is local, often burning, pain.Accompanying symptoms are allodynia, edema, hyperhidrosis, hypertrichosis, colouring of the skin, motor disturbances and in time atrophy of the involved tissue (skin, muscle, ;; jrf? bone).The symptoms are often disproportionate to the inciting evenr*'. .v q To improve clinical recognition of this disorder, and facilitate selection of more ••-;•-• general i/able samples for treatment outcome and basic science research the International Association for the Study of Pain (IASP) introduced a standardised CRPS I criteria''*.According to the IASP the diagnosis of CRPS I should be based on the following criteria:1.The presence of an initiating noxious event, or a cause of immobilisation.2. Continuing pain, allodynia.or hyperalgesia with which the pain is disproportionate to any inciting event.3. J-vidence at some time of edema, changes in skin blood (low, or abnormal sudomotor activity in the region of pain.4.This diagnosis is excluded by the existence of conditions that would otherwise account These criteria ore easy to handle and sufficient for clinical use.However, for scientific research they are too circumstantial and lack specificity.The external validity of the IASP criteria used as currently written may result in the over-diagnosis of CRPS r"-*>.As suggested by Bruehl and co-workers a more restricted definition, which combines the symptoms should be used for scientific studies'".They proposed the following modified research diagnostic criteria for CRPS 1:1. Continuing pain which is disproportionate to any inciting event.2. Must report at least one symptom in each of the four following categories Smwrv: reports of hyperesthesia.Kttwmo/w: reports of temperature asymmetry and/or skin colour changes and/or skin colour asymmetry..Vi«Aim/or/rr»p/iir: evidence of decreased range of motion and or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin).These modifications, based upon results of their factor unalytit he more specific than current IASP criteria, and may substantially improve the ability lo H discriminate accurately between C'RPS I and other types of neuropathic pain.w.i.EPIDEMIOLOGY The mean age of CRPS I (I and II) patients ranges from 36 to 42 years with a predominant For women (60% to 81%).The upper extremities are more often affected than the lower extremity.As mentioned before the aetiology of CRPS Is typically an injury: 16% after fracture, 10%-29% after sprain.3% to 24% post-surgery, 2% o 17% other causes, or of unknown aetiology**' *'.Veldman et al reported that the recurrence or 'spread' to involve another extremity or region to be 10%.He estimated the incidence of recurrence at 1.8% a year*".In a prospective study Maleki et al demonstrated that the mean onset of contiguous spread was 78 days; independent and mirror image spread was longer; 2.6 and 2.5 years respectively*''.MEASUREMENT Pain assessment Pain intensity is the most common pain dimension measured in both clinical work and treatment outcome research^.Normally pain ratings arc assessed using a 100 mm Visual Analogue Scale (VAS).which is anchored by 2 extremes of pain; "no pain" on the left and "the worst possible pain" on the right.A single rating of pain intensity is mostly used, however it is unlikely that a single rating is a reliable or valid indicant of average pain^'.One way to increase the validity of assessment of average pain is to increase the number of -7 -assessments".In chronic pain patients a single pain intensity rating is the least reliable and valid, while 3 measures of pain intensity a day over the course of 4 days has excellent internal consistency and validity^-**.It is articulated that patient may be able to assess their own average pain levels over a period of time simply by asking them to rate their pain "on average" at a single-point in time".In back pain patients it has been shown that a single rating of pain "on average" is an accurate estimate of "actual average" pain intensity measured over a course of 7 days"'.It is not clear whether this is also the case for CRPS I patients.Sensory and motor tents Hypocsthcsia and allodynia arc frequently present in CRPS I patients, and are among the diagnostic criteria"'••" Pin prick, light touch, mechanical and thermal stimulation are used to detect sensory disturbance.However, formal testing of skin thermal thresholds have so far failed to demonstrate typical abnormalities in CRPS I**-*".' Kcmlcr ct al developed a simple device to assess the function of the foot by testing separate tasks for each foot'*'.Range of Motion (ROM) is often used to test the functional gtAtC of both ihe Upper nnif lnw«T i»vlr<»mili«»o'*" Th*>»i> mtusuiva aiv fluttcvel MiDjCClfVC methods mul are patient and observer dependant.Therefore, drawing conclusions about the effectiveness of functional state of any given treatment may be questionable.Skin temperature measurements Skin temperature measurements by means of thermistors or thermography demonstrated that the temperature of the affected limbs is changed compared to the non-affected limbs'*--*'.However, the sensitivity and specificity of these tests has never been formally examined.Radiology On the side-comparing X-rays typically spotty osteoporotic changes can be found after 4 to 8 weeks^.However, these changes only occur in 40% of the cases.-8 -TREATMENT Rehabilitation Oerlemans et al demonstrated in their prospective controlled study that physical therapy is helpful in the management of pain and mobility restoration in CRPS I patients"-.In an evaluation of 145 patients physical therapy reduced the pain significantly*'.•• i Psychotherapy .; »*•{ The efficacy of psychotherapy, including cognitive behavioural therapy, stress management, coping skills, relaxation techniques, imagery, self-hypnosis and biofcedback techniques, in patients with chronic pain is documented in several controlled trials'**-•*.Therefore, psychotherapy is proposed for patients with CRPS I to assist in the general rehabilitation of the patients**.Pain management /ViarmtK-f>/«K«-/mi«w«v»/.The agents currently used in the treatment of CRPS I include: tricyclic antidepressants", anticonvulsants'*, radical scavengers'^, nonsteroidal antiinflammatory drugs (NSAIDs), calcium regulating drugs, corticosteroids, opioids, calcitonin, adrenoceptor antagonists and agonists, GABA agonists, NMDA-receptor antagonists'''.5vm/M)r/K7/r />/orfcv.Sympathetic block is performed by stellate ganglion block"*, epidurul administration of clonidine** and regional intravenous sympathetic blockade (RIS)'*.Agents used in RIS blockade include phentolamine'"'', reserpinc"", guanethidine"' "*, dropcridoP" and ketanserine"-".Although, there is a lack of prospective studies evaluating sympathetic