The changes of c-Fos expression by motor cortex stimulation in the deafferentation pain model.

The effect of motor cortex stimulation (MCS) therapy for deafferentation pain was evaluated based on c-Fos, a known pain marker. Nineteen mature cats weighing 1.5-3.5 kg were used. Cats were divided into three groups: a deafferentation pain group in which the left trigeminal ganglion was destroyed, an MCS group in which MCS was used following destruction of the trigeminal ganglion, and a control group. Sites and levels of c-Fos expression were examined immunohistochemically. The percentage of c-Fos-positive cells in the left spinal nucleus of the trigeminus, the bilateral insula, and the bilateral operculum increased in both the deafferentation pain and the MCS groups. There were no statistically significant differences between these groups. In the cingulate gyrus, the percentage of c-Fos-positive cells increased bilaterally in the deafferentation pain group and the MCS group, but the increase was greater in the MCS group. The increase in c-Fos-positive cells in the left spinal nucleus of the trigeminus in the deafferentation group may reflect reported electrical hyperactivity. The cingulate gyrus, insula, and parietal operculum were activated after deafferentation. This change (increase in c-Fos positive cells) is related to the development of deafferentation pain. Pain relief due to MCS is not dependent on the suppression of the activated left spinal nucleus of the trigeminus or the descending analgesic mechanism of the brain stem. Activation of the cingulate gyrus appears to be a factor in the analgesic mechanism of MCS.

Atypical odontalgia: an up-to-date view.

Atypical odontalgia (AO) is a little known chronic pain condition. It usually presents as pain in a site where a tooth was endodontically treated or extracted, in the absence of clinical or radiographic evidence of tooth pathology. It is a rare clinical challenge for most clinicians, which leads to the patients being referred to several specialists and sometimes undergoing unnecessary surgical procedures. The pain mechanisms involved in AO are far from clear, and numerous potential mechanisms have been suggested. Currently, the most accredited hypothesis is that AO is a neuropathic pain condition caused by deafferentation. The differential diagnosis of AO remains difficult, because it shares symptoms with many others pathologies affecting this area. Patients have difficulties accepting the AO diagnosis and treatment. As a result, they frequently change physicians, and may potentially also receive several invasive treatments, usually resulting in an aggravation of the pain. Although some patients do get complete pain relief following treatment, for most patients the goal should be to achieve adequate pain management. Currently, most management is based on expert opinion and case reports. More research and high quality randomized controlled trials are needed in order to develop evidence-based treatments, currently based on expert opinion or carried over from other neuropathic pain conditions in the orofacial region.

[Small fiber sensory neuropathies: contribution of laser evoked potentials]. / Neuropathies sensitives des petites fibres : intérêt des potentiels évoqués laser.

Standard neurophysiological techniques evaluate exclusively large myelinated fibers, but are not useful to explore sensory small fibers. Quantitative sensory tests have been developed to explore the thermal nociceptive function but this exploration is only subjective. Laser evoked potentials (LEPs) represent a noninvasive and objective test to explore thermal and nociceptive pathways. The clinical interest of LEPs have been assessed recently in the diagnosis of small fibers sensory neuropathies. In routine, the determination of detection and nociceptive thresholds, the analysis of N2P2 latencies and amplitudes enable demonstration of a dysfunction of A delta nerve fibers, to quantify these lesions and to determine whether the neuropathies are length-dependent or not. The LEP amplitude is negatively correlated to deafferentation. The interest of LEPs remained to be studied compared to skin biopsy.

Causalgia: a restatement.

Forty-eight cases of causalgia are described. The syndrome was caused by missile injury in 33 patients. There was a major arterial injury in 22 patients. Sympathetic block followed by sympathectomy abolished the pain in 11 of the first 14 patients in the series. Causalgia was cured by correcting the lesion of the nerve and of the adjacent axial artery in the subsequent 32 patients. The concept of complex regional pain syndrome Type 1 and Type 2 is challenged.

Peripheral median nerve stimulation for the treatment of iatrogenic complex regional pain syndrome (CRPS) type II after carpal tunnel surgery.

We report on the use and follow-up of direct peripheral nerve stimulation of the median nerve for the treatment of iatrogenic complex regional pain syndrome (CRPS). A 56-year-old woman presented with CRPS type II in the right forearm and hand, which had started after multiple carpal tunnel surgeries and had lasted for 2 years. The visual analogue scale (VAS) score was 8-10 out of 10. After a successful 15-day trial of median nerve peripheral nerve stimulation via a quadripolar lead in the right carpal tunnel space, an implantable pulse generator was inserted in the right infraclavicular space. The VAS score decreased to 1-2 out of 10 and the patient regained the ability to sleep. After 36 months of follow-up, the patient was still experiencing good pain relief without other treatment. We conclude that peripheral nerve stimulation is easy to use in pain management and could offer a valid treatment option for iatrogenic CRPS type II.

Dorsal root entry zone coagulation for treatment of deafferentation pain syndromes.

BACKGROUND: Deafferentation pain is a kind of chronic pain syndrome and hard to manipulate. To evaluate the effectiveness and safety of junctional dorsal root entry zone (DREZ) coagulation, 23 consecutive patients with intractable deafferentation pain syndrome were studied. METHODS: Twenty-three patients underwent junctional DREZ coagulation (C5-T1 for upper extremities and L2-S1 for lower extremities) under general anesthesia. The pain severity was evaluated by the short McGill pain questionnaire (MPQ) and the visual analog scale (VAS), and the depression and anxiety of patients were assessed by Hamilton rating scale for depression (HRSD), Hamilton anxiety scale (HAMA), self-rating anxiety scale (SAS) and self-rating depression scale (SDS). RESULTS: All the patients experienced significant pain reduction immediately after surgery. The scales of short MPQ and VAS at pre-operation, 6-month and 12-month follow-up were 31.5 +/- 3.4 and 8.8 +/- 1.5, 6.5 +/- 1.9 and 2.5 +/- 2.2, 7.1 +/- 2.1 and 2.9 +/- 1.9, respectively. The postoperative scores comparing to pre-operative scores showed a statistically significant difference (P < 0.01). The depression and anxiety state was also significantly relieved. At 12-month follow-up 6 patients had complete pain relief, 11 had excellent results with more than 75% pain relief, 17 had good results with more than 50% pain relief (73.9%). The main postoperative complications were transient slight hemiplegia (8), hypesthesia and paresthesia (15), a bearing down feeling of affected extremity (6), and deep sensory disability in the lower limbs (4) on the operated side. Because of the long time and prone position of the operation, 13 cases had a transient hyperalgesia in the upper chest. CONCLUSION: DREZ coagulation is a safe and effective procedure in the treatment of deafferentation pain syndromes.

Complex regional pain syndrome with special emphasis on the knee.

Complex regional pain syndrome is characterised by an exaggerated response to injury in a limb with intense prolonged pain, vasomotor disturbance, delayed functional recovery and trophic changes. This review describes the current knowledge of the condition and outlines the methods of treatment available with particular emphasis on the knee.

Motor cortex stimulation and neuropathic facial pain.

Trigeminal neuropathic pain is a syndrome of severe, constant facial pain related to disease of or injury to the trigeminal nerve or ganglion. Causes of this type of pain can include injury from sinus or dental surgery, skull and/or facial trauma, or intentional destruction for therapeutic reasons (deafferentation) as well as intrinsic pathological conditions in any part of the trigeminal system. Motor cortex stimulation (MCS) is a relatively new technique that has shown some promise in the treatment of trigeminal neuropathic pain. This technique has the potential to revolutionize the treatment of chronic pain. The authors present a review of the literature, focusing on surgical technique, device programming, safety, and efficacy, and suggest some initial guidelines for standardization of these aspects. It is important to evaluate MCS critically in a prospective, controlled fashion.

[Treatment of hand surgery patients in chronic pain]. / Therapie chronischer Schmerzpatienten in der Handchirurgie.

The treatment of hand surgery patients suffering from chronic pain requires an interdisciplinary procedure. An imbalance between nociception and antinociception can be seen as a reason for the chronification of pain. The complexity of the problem of chronic pain patients is marked by a wide variety of symptoms. Full diagnostic assessment to detect or to exclude other organic diseases is required. Rehabilitation to improve function and reduce pain intensity has priority. Our therapeutic strategy consists of intensive physiotherapy and analgesic drugs as well as a series of blockades with buprenorphine (Temgesic) of the ganglion stellatum (GLOA). This specific therapy achieved an improvement of the function of the upper extremity and a reduction of pain intensity. The majority of patients were satisfied with the outcome.

The characteristics of cyclical and non-cyclical mastalgia: a prospective study using a modified McGill Pain Questionnaire.

Breast pain (mastalgia) is a common condition (usually classified as cyclical or non-cyclical) the characteristics of which have never been studied using a standardized pain instrument. We have modified the short form of the McGill Pain Questionnaire (SF-MPQ) for the measurement of mastalgia, and have administered it to 271 women with breast pain and without breast cancer. The mean pain-rating index (sum of 15 descriptors of SF-MPQ) was similar between cyclical and non-cyclical pain, and was 12.0 (of 45) for the entire group. When compared to similar studies of pain at other sites, this falls in the same range as chronic cancer pain, and just below the pain of rheumatoid arthritis. Mean %VAS (visual analog scale) was 45.12 and mean %PPI (present pain index) was 39.9. Most women described their pain as 'heavy, aching and tender,' and these descriptors were given significantly higher ratings by women with cyclical pain. In women with non-cyclical mastalgia, the overall pain severity was related to the size of the painful area, and the steadiness of the pain, and the affective components were more prominent than in women with cyclical mastalgia. Thus, cyclical and non-cyclical mastalgia show some differences in their characteristics with substantial overlap. The total breast pain score was most efficiently estimated by a combination of the VAS, the PPI, and the quality of life questions (R2 = 0.96). Studies of breast pain should include both groups to better understand and characterize these differences, particularly with regard to a possible connection with breast cancer risk.

Dorsal root entry zone microcoagulation for spinal cord injury-related central pain: operative intramedullary electrophysiological guidance and clinical outcome.

OBJECT: Surgically created lesions of the spinal cord dorsal root entry zone (DREZ) to relieve central pain after spinal cord injury (SCI) have historically resulted in modest outcomes. A review of the literature indicates that fair to good relief of pain is achieved in approximately 50% of patients when an empirical procedure is performed. This study was undertaken to determine if intramedullary electrical guidance in DREZ lesioning could improve outcomes in patients with SCI-induced central pain. Additionally, electrical data were used to determine if the spinal cord could be somatotopically mapped with regard to this pain of central origin. METHODS: Forty-one patients with traumatic SCI and intractable central pain underwent DREZ lesioning in which intramedullary electrical guidance was conducted. In nine patients, recording of DREZ-related spontaneous electrical hyperactivity guided the lesioning process. In 32 patients, recording of DREZ-induced evoked electrical hyperactivity during transcutaneous C-fiber stimulation (TCS) additionally guided lesioning. The follow-up period ranged from 1 to 7 years. The analyzed electrical data allowed for somatotopic mapping of the spinal cord. CONCLUSIONS: Intramedullary electrical guidance of DREZ lesioning substantially improves pain outcomes in patients with traumatic SCI-induced central pain, compared with an empiric technique. The best outcome occurs when DREZ-related spontaneous electrical hyperactivity and evoked hyperactivity during TCS are both used to guide the DREZ lesioning procedure. With such guidance, 100% relief of pain was achieved in 84% of patients and 50 to 100% relief of pain in 88%. Somatotopic mapping of the electrical data led to a proposed pain mechanism for below-level pain, implicating the sympathetic nervous system.

Central neuroplasticity and pathological pain.

The traditional specificity theory of pain perception holds that pain involves a direct transmission system from somatic receptors to the brain. The amount of pain perceived, moreover, is assumed to be directly proportional to the extent of injury. Recent research, however, indicates far more complex mechanisms. Clinical and experimental evidence shows that noxious stimuli may sensitize central neural structures involved in pain perception. Salient clinical examples of these effects include amputees with pains in a phantom limb that are similar or identical to those felt in the limb before it was amputated, and patients after surgery who have benefited from preemptive analgesia which blocks the surgery-induced afferent barrage and/or its central consequences. Experimental evidence of these changes is illustrated by the development of sensitization, wind-up, or expansion of receptive fields of CNS neurons, as well as by the enhancement of flexion reflexes and the persistence of pain or hyperalgesia after inputs from injured tissues are blocked. It is clear from the material presented that the perception of pain does not simply involve a moment-to-moment analysis of afferent noxious input, but rather involves a dynamic process that is influenced by the effects of past experiences. Sensory stimuli act on neural systems that have been modified by past inputs, and the behavioral output is significantly influenced by the "memory" of these prior events. An increased understanding of the central changes induced by peripheral injury or noxious stimulation should lead to new and improved clinical treatment for the relief and prevention of pathological pain.

Neurological findings in complex regional pain syndromes--analysis of 145 cases.

Early diagnosis is a prerequisite for a successful treatment of complex regional pain syndrome (CRPS). In order to describe neurological symptoms which characterize CRPS, we evaluated 145 patients prospectively. Two-thirds of these were women, the mean age at time of investigation was 50.4 years. CRPS followed limb trauma, surgery and nerve lesion. Employing the current IASP criteria 122 patients were classified as CRPS I and 23 as CRPS II. All patients were assessed clinically pain was quantified using the McGill pain questionnaire, skin temperature was measured by an infrared thermometer and a subgroup of 57 patients was retested in order to determine thermal thresholds (QST). Of our patients 42% reported stressful life events in a close relationship to the onset of CRPS and 41% had a history of chronic pain before CRPS. The latter group of patients gave a higher rating of CRPS pain (P<0.05). The major symptoms were pain at rest in 77% and hyperalgesia in 94%. Typical pain was deep in the limb having a tearing character. Patients getting physical therapy had significantly less pain than those without (P<0.04). Autonomic signs were frequent (98%) and often changed with the duration of CRPS. Skin temperature was warmer in acute and colder in chronic stages (P<0.001). Likewise edema had a higher incidence in acute stages (P<0.001). We found no correlation between pain and autonomic dysfunction. Motor dysfunction (present in 97%) included weakness, tremor, exaggerated tendon reflexes, dystonia or myoclonic jerks. QST revealed increased warm perception thresholds (P<0.02) and decreased cold pain thresholds (P<0.03) of the affected limb. The detailed knowledge of clinical features of CRPS could help physicians early to recognize the disease and thus to improve therapy outcome.

Different strains and substrains of rats show different levels of neuropathic pain behaviors.

This study compared and contrasted the manifestation of neuropathic pain behaviors in several strains of rats. These included ACI, Brown-Norway, Fischer 344, Lewis, Long-Evans, Sprague-Dawley, and Wistar-Furth, all obtained from Harlan Sprague-Dawley Inc. Comparison was also made between two substrains of Sprague-Dawley rats: one from Harlan and the other from Sasco. Neuropathic injury was produced by tightly ligating the left L5 and L6 spinal nerves with the animals under halothane anesthesia. Tests were conducted for 2 weeks to examine behavioral signs representing mechanical allodynia, cold allodynia, and spontaneous pain. There was no difference between strains in any of the tested behaviors before surgery. After neuropathic injury, rats in most groups developed high levels of behavioral signs of various components of neuropathic pain; however, some strains of rats showed weak behavioral signs of neuropathic pain. When a comparison was made between two substrains of Sprague-Dawley rats from two different sources, the ones from Sasco showed weaker behavioral signs than those from Harlan. When comparisons were made between different strains of rats from the same source (Harlan), Brown-Norway and Long-Evans rats showed the smallest magnitude of neuropathic pain behaviors. The data indicate that different strains and substrains of rats display different degrees of pain behaviors, suggesting that strains and substrains are important variables in the development of neuropathic pain after peripheral nerve injury.

Adrenergic sensitivity of the sensory receptors modulating mechanical allodynia in a rat neuropathic pain model.

This study focuses on changes in adrenergic sensitivity in untransected sensory axons that innervate an area of skin made neuropathic by transection of neighboring nerves. The segmental nerve injury model is favorable for this since all axons in the L5 and L6 nerves are transected whereas the L4 axons are intact. Earlier findings are that pain behaviors develop after this injury and that these behaviors are ameliorated by sympathectomy. The present study shows that behavior indicating mechanical allodynia can be rekindled after sympathectomy by intradermal norepinephrine and alpha-2 but not alpha-1 adrenergic ligands and the rekindling can be blocked by alpha-2 but not alpha-1 adrenergic antagonists. By contrast neither intradermal norepinephrine nor other adrenergic agonists or antagonists have any demonstrable effects in the normal or after either neuropathic surgery or sympathectomy alone. These data suggest that the combination of neuropathic surgery and sympathectomy results in an upregulation of active alpha-2 adrenergic receptors on the undamaged sensory axons that provide the remaining sensory innervation to a neuropathic area partially denervated by segmental nerve lesions. These changes on undamaged axons presumably compliment similar changes on the transected axons and, thus play a role in the development of neuropathic pain.

Nerve injury increases an excitatory action of neuropeptide Y and Y2-agonists on dorsal root ganglion neurons.

Damage to sensory nerves invokes the expression of neuropeptide Y in the cell bodies of sensory neurons in dorsal root ganglia. We therefore compared the action of this peptide on control dorsal root ganglia neurons with its action on neurons from animals in which the sciatic nerve had been cut. Neuropeptide Y (0.1-1.0 microM) increased the excitability of 24% of control neurons and its effect was stronger and more cells (56%) were affected after axotomy. Increased excitability was mediated via a Y2-receptor and resulted from attenuation of Ca2+-sensitive K+-conductance(s) secondary to suppression of N-type Ca2+ channel current. Y1-agonists potentiated L-type Ca2+ channel current in control neurons without altering excitability. This Y1-effect was attenuated whereas effects mediated via Y2-receptors were enhanced after axotomy. No evidence was found for involvement of Y4- or Y5-receptor subtypes in the actions of neuropeptide Y either on control or on axotomized dorsal root ganglion neurons. It is concluded that neuropeptide Y increases the excitability of sensory neurons by interacting with a Y2-receptor and thereby decreasing N-type Ca2+ channel current and Ca2+-sensitive K+-conductance(s). When peripheral nerves are damaged, dorsal root ganglion neurons start to express neuropeptide Y and its excitatory Y2-excitatory effects are enhanced. The peptide may therefore contribute to the generation of aberrant sensory activity and perhaps to the etiology of injury-induced neuropathic pain.

Increase of interleukin-6 mRNA in the spinal cord following peripheral nerve injury in the rat: potential role of IL-6 in neuropathic pain.

Interleukin-6 (IL-6) is a multifunctional cytokine whose actions include modulation of proliferation, differentiation, and maturation of hemapoietic progenitors and other cell lineages; growth regulation of certain carcinoma cell lines; and control of cellular metabolic activities. Initially described in terms of its activities in the immune system and inflammation, accumulating evidence supports an essential role of IL-6 in the development, differentiation, regeneration and degeneration of neurons in the peripheral and central nervous system. We have previously demonstrated that immunoreactive-like IL-6 protein is significantly elevated in the spinal cord in response to peripheral nerve injury that results in neuropathic pain behaviors in the rat. In the current study, our objective was to determine if the source of IL-6 protein was endogenous to the central nervous system by measuring any detectable increases in spinal IL-6 mRNA expression following established mononeuropathy procedures associated with neuropathic pain: spinal nerve cryoneurolysis (SPCN) or spinal nerve tight ligation (SPTL). Using in situ hybridization and a digoxigenin-labeled oligonucleotide, IL-6 mRNA in neurons was significantly elevated at 3 and 7 days post SPCN and 7 days post SPTL in both dorsal and ventral horns. The cellular localization of the IL-6 mRNA expression was predominately neuronal as confirmed by NeuN serial staining. For example, in the SPCN 7 day group, IL-6 mRNA cell profiles in the ipsilateral dorsal horn were significantly different from the normal group (38.7+/-12.8 vs. 4.89+/-1.6, p<0.001). These data demonstrate the central, spinal production of a proinflammatory cytokine in response to a peripheral nerve injury. In addition, these results add to the growing body of literature implicating these immune products, cytokines, as potential neuromodulators/neurotransmitters and provides further evidence for their role in the nociceptive processing which leads to chronic pain.