Peripheral Nerve Inflammation Research Articles

Intravenous immunoglobulin for Guillain-Barré syndrome.

Guillain-Barré syndrome is an acute, paralysing, inflammatory peripheral nerve disease. Intravenous immunoglobulin purified from donated blood is beneficial in other autoimmune diseases. We aimed to determine the efficacy of intravenous immunoglobulin for treating Guillain-Barré syndrome. We searched the Cochrane Neuromuscular Disease Group register (search updated 11 February 2003), MEDLINE and EMBASE (from January 2000 to February 2003) using Guillain-Barré syndrome and acute polyradiculoneuritis as the search terms. We also searched bibliographies of trials and made contact with their authors and other experts. We included all randomised and quasi-randomised trials. Two reviewers examined the titles and abstracts of all the papers retrieved by the search, extracted the data and assessed the quality of the trials independently. Two trials comparing intravenous immunoglobulin with supportive treatment were inadequate to establish its value. Another Cochrane systematic review has shown that plasma exchange hastens recovery. We found six randomised trials that compared intravenous immunoglobulin with plasma exchange. In a meta-analysis of five trials involving 536, mostly adult, participants who were unable to walk unaided and had been ill for less than two weeks. The primary outcome measure in this review was the change in a seven grade disability scale four weeks after randomisation. The weighted mean difference of this measure was not statistically significant, being only 0.04 (95% CI -0.26 to 0.19) of a disability grade more improvement in the intravenous immunoglobulin group than the plasma exchange group. There were also no statistically significant differences in time to walk unaided, mortality, and proportion of participants unable to walk without aid after a year. One trial involving 249 participants compared plasma exchange followed by intravenous immunoglobulin with plasma exchange alone, and another involving 37 participants compared immunoabsorption followed by intravenous immunoglobulin with immunoabsorption alone. Neither revealed significant extra benefit from intravenous immunoglobulin. One study of only 39 participants showed a trend towards more improvement with high-dose compared with low-dose intravenous immunoglobulin. Although there are no adequate comparisons with placebo, intravenous immunoglobulin hastens recovery from Guillain-Barré syndrome as much as plasma exchange. Giving intravenous immunoglobulin after plasma exchange is not significantly better than plasma exchange alone. Randomised trials are needed to decide the effect of intravenous immunoglobulin in children, in adults with mild disease and in adults who start treatment after more than two weeks.

Induction of neuropeptide gene expression and blockade of retrograde transport in facial motor neurons following local peripheral nerve inflammation in severe combined immunodeficiency and BALB/C mice

Peripheral nerve inflammation is a common clinical problem that accompanies nerve injury and several diseases including Guillain-Barré syndrome and acute and chronic inflammatory demyelinating polyneuropathy. To determine if neuropeptides are induced in motor neurons after inflammation and to study the mechanisms involved, a nerve cuff soaked in complete Freund's adjuvant (CFA) was applied locally to the facial nerve of Balb/C mice. This procedure resulted in an influx of lymphocytes and macrophages to the affected area and a blockade of retrograde axonal transport distal, but not proximal, to the site of application. The same treatment resulted in a strong ipsilateral induction of pituitary adenylyl cyclase activating peptide (PACAP) gene expression in motor neurons in the facial motor nucleus. Because the changes could have occurred due to the loss of target-derived factors or to the production of new factors by immune cells, we studied the effect of the inflammatory stimulus on PACAP mRNA in mice with severe combined immunodeficiency (SCID). As expected, SCID mice showed a severely reduced influx of T-lymphocytes but not macrophages to the peripheral nerve. Moreover, although retrograde transport distal to the inflammation site was blocked similarly in control and SCID mice, the number of motor neurons expressing PACAP mRNA after CFA application was significantly reduced in SCID mice. The data indicate that the induction of PACAP mRNA during nerve inflammation requires the involvement of lymphocytes. However, because the induction of PACAP gene expression was only partially blocked in SCID mice, macrophages, loss of target-derived factors, or other mechanisms may also contribute to the upregulation of PACAP gene expression in motor neurons after nerve inflammation.

What do we know about the state of chronic pain?

Chronic pain syndromes are characterized by altered neuronal excitability in the pain matrix. The ability to rapidly acquire and store memory of aversive events is one of the basic principles of nervous systems throughout the animal kingdom. These neuroplastic changes take place e. g. in the spinal cord, in thalamic nuclei and cortical and subcortical (limbic) areas integrating pain threshold, intensity and affective components. Chronic inflammation or injury of peripheral nerves evokes the reorganisation of cortical sensory maps. Neurons conveying nociceptive information are controlled by various sets of inhibitory interneurons. The discharge activity of these interneurons counteracts long-term changes in the pain matrix following nociceptor activation, i. e. it prevents the transition of acute pain signaling to chronic pain states. Our most recent research suggests that pain states may be sensitive to novel families of agents and therapeutic measures not predicted by traditional preclinical pain models as well as human pain states. The endogenous cannabinoid system plays a central role in the extinction of aversive memories. We propose that endocannabinoids facilitate extinction of aversive memories via their selective inhibitory effects on GABAergic networks in the amygdala.

The effects and reality of WRULD (work-related upper limb disorder)

“There is substantial literature denying the existence of non-specific WRULD, largely because of the absence of tissue pathology. In general terms, therefore, if the medical model of injury (damage, followed by repair, healing and, finally, cure) is invoked then non-specific WRULD cannot be identified as a disease” (www.hse.gov.uk). Evidence shows an alarmingly high percentage of sonographers/sonologists worldwide are experiencing, or have experienced at some time, a work-related muskuloskeletal problem. Repetitive overloading of the upper body muscles results in rapid fatigue. The ultimate effect of this persistent abuse is “work- related upper limb disorder” (WRULD). The severity of any injury can range from a simple ache to potential loss of function of the upper limb. Pathological problems range from tendinopathy, spinal and peripheral nerve inflammation, muscle and joint disorders, and vision impairment. Diffuse pain is commonly reported (“non-specific arm pain”) or myofascial pain, which is pain in the muskuloskeletal system without any obvious cause. The impact of WRULD is that simple tasks cannot be performed and that continuing to work becomes increasingly difficult. This limitation and persistent pain can then result in depression. In UK ultrasound, we are not taking pre-emptive action by thorough planning of ergonomics, workload, and most importantly, staff awareness. We wait until it has happened. This presentation is designed to warn that this debilitating problem can affect anyone who scans and to give some advice on how to recover.

Glutamate-induced currents reveal three functionally distinct NMDA receptor populations in rat dorsal horn – effects of peripheral nerve lesion and inflammation

The importance of the N-methyl- D-aspartate (NMDA) receptor in various painful conditions is well established. The effects of peripheral nerve lesion or joint inflammation, as models of different pain states, on NMDA receptor-mediated currents and NMDA receptor subunit mRNA expression were therefore studied in acutely dissociated neurones from the rat spinal cord dorsal horn. In the neuronal population from control rats, all four NR2 subunits and both NR1 splice variants assayed were detected. A majority of neurones expressed mRNA for more than one NR2 subunit, and some neurones expressed all four NR2 subunits as well as both NR1 splice variants. The NR2B subunit was the most commonly expressed, while the NR2C was the rarest. Following nerve lesion, fewer neurones expressed NR2A compared to the control. The dose–response curve for glutamate-evoked NMDA receptor-mediated currents in the neurones was best described by a three-component fit, suggesting that three functionally distinct NMDA receptor populations are present in the dorsal horn. Minor changes in the dose–response curve after nerve lesion could not be ascribed with certainty to the lesion. Changes in other parameters of NMDA receptor-mediated currents were observed neither after nerve lesion nor after joint inflammation. In summary, the present work demonstrates that single dorsal horn neurones express mRNA for several NMDA receptor subunits. The glutamate dose–response curves indicate that there are three major types of NMDA receptors present in dorsal horn neurones. We also report a reduced expression of NR2A following peripheral nerve lesion.

Plasma exchange for Guillain-Barré syndrome.

Guillain-Barré syndrome is an acute symmetric, usually ascending and usually paralysing illness, due to inflammation of peripheral nerves. It is thought to be caused by autoimmune factors, such as antibodies. Plasma exchange removes antibodies and other potentially injurious factors from the blood stream. It involves connecting the patient's blood circulation to a machine which exchanges the plasma for a substitute solution, usually albumin. Several studies have evaluated plasma exchange for Guillain-Barré syndrome. To systematically review the evidence concerning the efficacy of plasma exchange for treating Guillain-Barré syndrome. Search of the Cochrane Neuromuscular Disease Trial Register for randomised trials concerning plasma exchange in Guillain-Barré syndrome, search of the bibliographies of identified papers and enquiry from the authors of the papers. Randomised and quasi-randomised trials of plasma exchange versus sham exchange or supportive treatment. Potentially relevant papers were scrutinised by two reviewers and the selection of eligible studies was agreed by them and a third reviewer. Data were extracted by one reviewer and checked by a second reviewer. Some missing data were obtained from the authors of studies. Six eligible trials concerning 649 patients were identified, all comparing plasma exchange versus supportive treatment alone. Primary outcome measures ~bullet~Time to recover walking with aid In the only two trials for which this measure was reported, the median time to recover this ability was faster in the plasma exchange than the control group. ~bullet~Time to onset of motor recovery in mildly affected patients In the one trial for which this measure was available, the time was significantly shortened in the plasma exchange group. Secondary outcome measures ~bullet~Improvement in disability grade at four weeks In five trials, there were significantly more patients who had improved by one disability grade or more in the plasma exchange group as compared to the control group. Patients treated with plasma exchange fared significantly better in the following secondary outcome measures: time to recover walking without aid, percentage of patients requiring artificial ventilation, duration of ventilation, full muscle strength recovery after one year, and severe sequelae after one year. There were less patients with infectious events and cardiac arrhythmias in the plasma exchange than the control group. Subgroup analyses Plasma exchange was beneficial in patients with mild, moderate and severe (needing ventilation) Guillain-Barré syndrome. It was beneficial in patients with a disease duration of seven or less days and also in those with disease lasting more than seven days. However, in the only trial that enrolled patients up to 30 days from disease onset, the benefit of plasma exchange in patients treated after seven days was less apparent. Type of treatment Single studies showed that two plasma exchanges were significantly superior to none for mild Guillain-Barré syndrome and four to two for moderate Guillain-Barré syndrome, but that six were not superior to four for severe Guillain-Barré syndrome requiring ventilation. One study suggested that continuous flow plasma exchange was significantly superior to intermittent flow. Another study found no significant difference between the two techniques. The same study found a significantly higher rate of adverse events with fresh frozen plasma as the replacement fluid than albumin. Plasma exchange compared with cerebrospinal fluid filtration A single trial comparing these two treatments did not show any difference in outcomes but was too small to demonstrate equivalence. Plasma exchange is the first and only treatment that has been proven to be superior to supportive treatment alone in Guillain-Barré syndrome. Consequently, plasma exchange should be regarded as the treatment against which new treatments, such as intravenous immunoglobulin, should be judged. In mild Guillain-Barré syndrome two sessions of plasma exchange are superior to none. In moderate Guillain-Barré syndrome four sessions are superior to two. In severe Guillain-Barré syndrome six sessions are no better than four. Continuous flow plasma exchange machines may be superior to intermittent flow machines and albumin to fresh frozen plasma as the exchange fluid. Plasma exchange is more beneficial when started within seven days after disease onset rather than later, but was still beneficial in patients treated up to 30 days after disease onset. The value of plasma exchange in children less than 12 years old is not known. There is insufficient evidence to determine whether cerebrospinal fluid filtration is equivalent to plasma exchange.

Corticosteroids for chronic inflammatory demyelinating polyradiculoneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy is a peripheral neuropathy caused by peripheral nerve inflammation probably due to autoimmunity and would be expected to benefit from corticosteroids. Non-randomised studies suggest that corticosteroids are often beneficial. To evaluate the efficacy of corticosteroids for treating chronic inflammatory demyelinating polyradiculoneuropathy. Search of the Cochrane Neuromuscular Disease Group register for randomised trials of corticosteroids treatment for chronic inflammatory demyelinating polyradiculoneuropathy and enquiry from subject experts. Types of studies: All randomised or quasi-randomised trials Types of Participants: All patients with chronic inflammatory demyelinating polyradiculoneuropathy who were diagnosed by an internationally accepted definition. Types of interventions: Treatment with any form of corticosteroids or adrenocorticotropic hormone. Types of outcome measures: Change in disability 12 weeks after randomisation. 1. Change in impairment 12 weeks after randomisation. 2. Change in maximum motor nerve conduction velocity or compound muscle action potential amplitude after 12 weeks. 3. Side effects of corticosteroids. One author extracted the data and the other checked them. We identified one randomised controlled trial, an open study in which 19 corticosteroids treated patients showed more improvement in impairment than 16 untreated controls after 12 weeks. Experience from large non-randomised studies suggests that steroids are beneficial. A single randomised controlled trial with 35 participants provided weak evidence to support the conclusion from non-randomised studies that oral corticosteroids reduce impairment in chronic inflammatory demyelinating polyradiculoneuropathy. Corticosteroids are known to have serious long term side effects. The long term risk and benefits have not been adequately studied.

Beyond neurons: evidence that immune and glial cells contribute to pathological pain states.

Chronic pain can occur after peripheral nerve injury, infection, or inflammation. Under such neuropathic pain conditions, sensory processing in the affected body region becomes grossly abnormal. Despite decades of research, currently available drugs largely fail to control such pain. This review explores the possibility that the reason for this failure lies in the fact that such drugs were designed to target neurons rather than immune or glial cells. It describes how immune cells are a natural and inextricable part of skin, peripheral nerves, dorsal root ganglia, and spinal cord. It then examines how immune and glial activation may participate in the etiology and symptomatology of diverse pathological pain states in both humans and laboratory animals. Of the variety of substances released by activated immune and glial cells, proinflammatory cytokines (tumor necrosis factor, interleukin-1, interleukin-6) appear to be of special importance in the creation of peripheral nerve and neuronal hyperexcitability. Although this review focuses on immune modulation of pain, the implications are pervasive. Indeed, all nerves and neurons regardless of modality or function are likely affected by immune and glial activation in the ways described for pain.

Polygenic control of autoimmune peripheral nerve inflammation in rat

Experimental autoimmune neuritis (EAN) is the principal animal model for Guillain–Barré syndrome (GBS), an inflammatory disease of the peripheral nervous system. Little is known on the genetic regulation of these diseases. We provide the first genetic linkage analysis of EAN. Susceptibility to EAN in a rat F2 population segregated with high levels of anti-PNM IgG, as well as IgG2b and IgG2c isotype levels, which support that disease genes regulate preferential Th1/Th2 differentiation. Linkage analysis demonstrated co-localization of EAN loci with reported susceptibility loci for experimental arthritis and/or encephalomyelitis and a new region on chromosome 17. Further dissection of these loci may disclose disease pathways in GBS.

Differential usage of multiple brain-derived neurotrophic factor promoter in rat dorsal root ganglia following peripheral nerve injuries and inflammation

The brain-derived neurotrophic factor (BDNF) may act as either an autocrine or paracrine survival factor for the dorsal root ganglion (DRG) neurons and may also serve as a neurotransmitter or neuromodulator within the dorsal horn of the spinal cord. The rat BDNF gene consists of four short 5′ exons linked to separate promoters and one 3′ exon encoding the mature BDNF protein. An exon-specific reverse transcription–polymerase chain reaction analysis was used to study the differential utilization of multiple promoters in the DRG following unilateral sciatic axotomy, dorsal rhizotomy and peripheral inflammation. The exon I transcript showed the highest induction rate with the ipsilateral expression elevated 4.3–5.8 times that of contralateral expression. Both exon II and III mRNAs showed a smaller increase 1 day after the three kinds of stimuli. In addition, exon IV mRNA transcription increased slightly only after rhizotomy, but not after axotomy and peripheral inflammation after 1 day. Furthermore, the elevated exon I mRNA levels 1 day after rhizotomy were sustained for up to 7 days. In contrast, those of the exon I mRNA after axotomy had declined 2.8 times the control level after 7 days. These findings suggest that the promoter linked to exon I may provide a major regulatory point of BDNF mRNA expression by peripheral nerve injuries and inflammation. In addition, both exon I and IV mRNA expression may show different temporal activation patterns according to the types of injury.

Changes in post-tetanic potentiation of A-fiber dorsal horn field potentials parallel the development and disappearance of neuropathic pain after sciatic nerve ligation in rats

Significant plastic changes in spinal nociceptive processing appear to accompany peripheral nerve injury or inflammation. Using a well-established model of neuropathic pain, we have recently reported that loose ligation of the sciatic nerve was accompanied by a long-lasting post-tetanic potentiation of sciatic-evoked A-fiber superficial dorsal horn field potentials. In the present study we demonstrate that the typical disappearance of thermal hyperalgesia as a behavioral sign of neuropathic pain several weeks after loose sciatic nerve ligation is accompanied by the loss of the long-lasting potentiation. These data suggest that a significant but reversible shift in the processing of sensory information in the spinal dorsal horn follows peripheral nerve injury, and lend further support to the notion that long-lasting synaptic plasticity may contribute to the development of neuropathic pain.

Mechanism for chronic pain generation

Neuropathic pain and the other abnormalities of sensation induced by axon injury or by peripheral nerve inflammation should result from functional compensations of the injured neurons during their regeneration. Ectopic distribution of proteins related to Na+, K+ and Ca2+ channels as well as of receptors on both membranes of injured axon and its cell body becomes a main pacemaker from which spontaneous ectopic afferent of primary sensatory neurons and crosstalk between neurons occur. Abnormal ectopic afferent activities lead to disorders of the sensation, such as hyperalgesia, allodynia, spontaneous pain and paraesthesia. Administration of some ion channel agents and/or α2-adrenergic blockers has shown efficiency in preventing neuropathic pain development and in relieving neuropathic pain.

Distribution and regulation of α2-adrenoceptors in rat dorsal root ganglia

Using in situ hybridization with riboprobes the distribution of α2A-, α2B- and α2C-adrenoceptor mRNAs were studied in normal rat dorsal root ganglia and after unilateral peripheral nerve injury (total nerve transection) or inflammation. The most common adrenoceptor mRNA was of the α2C subtype (almost 80% of all neuron profiles) followed by the α2A subtype (almost 20%), whereas α2B-adrenoceptor mRNA was only found in small numbers of neuron profiles. The most dramatic effect of peripheral nerve injury was observed for the α2A-adrenoceptor mRNA, which increased to 45% of all neuron profiles. In contrast, α2C adrenoceptor mRNA showed a small decrease in this situation. Carrageenan-induced peripheral inflammation did not affect the percentage of α2A- or α2C-adrenoceptor mRNA-positive profiles. These findings suggest that, if any of the α2 adrenoceptor, the α2A subtype represents the most likely candidate in DRG neurons to be involved in sympathetically maintained pain.

Morphological changes in the skin during experimental allergic encephalomyelitis and multiple sclerosis: bases for new diagnostic test.

Skin specimen from the medial malleolar area of patients with multiple sclerosis and guinea pigs with experimental allergic encephalomyelitis were examined by light and electron microscopy. Demyelination, inflammation, and dystrophic changes in peripheral nerves and skin correlating with clinical manifestations were revealed in both sclerosis and encephalomyelitis. Maximum changes were revealed in nerve-associated cells (Merkel cells), Langerhans cells reflecting inflammation intensity, and fibroblasts responsible for nerve integrity and resistance against external stimuli.

Effect of morphine on cholecystokinin and μ-opioid receptor-like immunoreactivities in rat spinal dorsal horn neurons after peripheral axotomy and inflammation

In order to further investigate the interaction between the octapeptide cholecystokinin and opioid analgesia in the spinal cord we used double-colour immunofluorescence to examine the anatomical distribution of cholecystokinin and μ-opioid receptors in the dorsal horn, as well as the effect of morphine on cholecystokinin- and μ-opioid receptor-like immunoreactivities following peripheral nerve injury and inflammation. μ-opioid receptor-like immunoreactivity was present in 65.6% of cholecystokinin-positive neurons in laminae I and II of rat spinal cord. Conversely, 40.4% of μ-opioid receptor-positive neurons contained cholecystokinin-like immunoreactivity. Systemic application of morphine (1, 3 or 10 mg/kg; i.v.) after sciatic nerve section significantly, but reversibly, decreased μ-Opioid receptor-like immunoreactivity in the medial half of lamina II in segment L5 of the ipsilateral dorsal horn, and cholecystokinin-like immunoreactivity was also markedly reduced in the same region. These effects were dose- and time-dependent and could be prevented by naloxone preadministration. In contrast, no significant change in the pattern of distribution or intensity of μ-opioid receptor- and cholecystokinin-like immunoreactivities was observed in intact rats or during peripheral inflammation. These results provide a cellular basis for the interaction of μ-opioid receptors and cholecystokinin at the spinal level by showing a high degree of co-existence of these two molecules in local interneurons, and also show that morphine can induce rapid and short lasting effects on μ-opioid receptors after peripheral nerve injury. The results contribute to our understanding of how endogenous cholecystokinin reduces the analgesic effect of morphine.

Expression of alpha2-adrenergic receptors in rat primary afferent neurones after peripheral nerve injury or inflammation.

1. Immunocytochemistry with polyclonal antibodies directed against specific fragments of intracellular loops of alpha2A- and alpha2C-adrenergic receptors (alpha2A-AR, alpha2C-AR) was used to explore the possibility that expression of these receptors in dorsal root ganglion (DRG) neurones of rat alters as a result of peripheral nerve injury or localized inflammation. 2. Small numbers of neurones with positive alpha2A-AR immunoreactivity (alpha2A-AR-IR) were detected in DRG from normal animals or contralateral to nerve lesions. In contrast, after complete or partial sciatic nerve transection the numbers of ipsilateral L4 and L5 DRG somata expressing alpha2A-AR-IR sharply increased (>5-fold). There was no discernible change in the number of DRG neurones exhibiting alpha2A-AR-IR innervating a region in association with localized chemically induced inflammation. 3. After nerve injury, double labelling with Fluoro-Gold, a marker of retrograde transport from transected fibres, or by immunoreactivity for c-jun protein, an indicator of injury and regeneration, suggested that many of the neurones expressing alpha2A-AR-IR were uninjured by the sciatic lesions. 4. In general the largest proportionate increase in numbers of neurones labelled by alpha2A-AR-IR after nerve lesions appeared in the medium-large diameter range (31-40 microm), a group principally composed of cell bodies of low threshold mechanoreceptors. The number of small diameter DRG neurones labelled by alpha2A-AR-IR, a category likely to include somata of nociceptors, also increased but proportionately less. 5. Relatively few DRG neurones exhibited alpha2C-AR-IR; this population did not appear to change after either nerve lesions or inflammation. 6. These observations are considered in relation to effects of nerve injury on excitation of primary afferent neurones by sympathetic activity or adrenergic agents, sympathetically related neuropathy and reports of sprouting of sympathetic fibres in DRG.

Expression of α 2 -adrenergic receptors in rat primary afferent neurones after peripheral nerve injury or inflammation

Expression of α 2 -adrenergic receptors in rat primary afferent neurones after peripheral nerve injury or inflammation

Galanin in somatosensory function.

Galanin-like immunoreactivity and galanin receptors are found in dorsal root ganglion (DRG) cells and in dorsal horn interneurons, suggesting that this neuropeptide may have a role in sensory transmission and modulation at the spinal level. Expression of galanin or galanin receptors in the DRG and spinal cord are altered, sometimes in a dramatic fashion, by peripheral nerve injury or inflammation. Under normal conditions, galanin occurs in a small population of primary sensory neurons as well as in spinal interneurons. However, following peripheral nerve injury or inflammation, expression of galanin in primary afferents and spinal cord is upregulated. We examined the role of galanin in spinal processing of nociceptive information under normal and pathologic conditions in a large series of electrophysiologic and behavioral studies. Results suggest that under normal conditions galanin exerts tonic inhibition of nociceptive input to the central nervous system. After peripheral nerve injury the inhibitory control exerted by endogenous galanin, probably released from DRG neurons, is increased. During inflammation, galanin presumably released from dorsal horn interneurons also exerts an inhibitory function. Thus, stable galanin agonists may be useful in the treatment of inflammatory and neuropathic pain.

Anti-hyperalgesic and anti-allodynic effects of intrathecal nociceptin/orphanin FQ in rats after spinal cord injury, peripheral nerve injury and inflammation

We examined the effects of intrathecal nociceptin, the endogenous ligand for the orphan opioid receptor-like receptor, on abnormal pain-related behaviors in rats after carrageenan-induced inflammation and photochemically-induced peripheral nerve or spinal cord ischemic injury. Intrathecal nociceptin dose-dependently alleviated mechanical and cold allodynia-like behavior in the two models of neuropathic pain. The heat hyperalgesia associated with peripheral inflammation was also significantly reduced, although the efficacy of the anti-hyperalgesic effect of nociceptin in the inflammation model was decreased. Intrathecal nociceptin also induced significant antinociceptin on the tail-flick test in all three groups of rats. However, the antinociceptive effect of nociceptin was significantly reduced in rats with peripheral nerve injury. These results indicated that spinally administered nociceptin has anti-allodynic and anti-hyperalgesic effects in animal models of tonic or chronic pain of different origins. Peripheral inflammation and nerve injury may induce spinal plasticity which leads to altered potency and efficacy of nociceptin.

Soluble complement receptor 1 (sCR1) is not as effective as cobra venom factor in the treatment of experimental allergic neuritis

To further investigate the role of complement activation in Experimental Allergic Neuritis (EAN), the effect of systemic complement blockade by soluble CR1 (sCR1) was compared to complement depletion by Cobra Venom Factor (CVF) in EAN rats immunized with bovine peripheral nerve myelin. EAN rats treated with CVF (n = 10) had significantly reduced clinical scores compared to rats treated with sCR1 (n = 9) or saline (n = 10) (score: sCR1 0.66 ± 0.7; CVF 0; saline 0.6 ± 0.8; mean ± SD). CVF treatment more effectively decreased inflammation and demyelination compared to sCR1 treatment which had only a partial effect (inflammation: sCR1 1.8 ± 1.4; CVF 0.3 ± 0.7; saline 1.9 ± 1.2; demyelination; sCR1 1.3 ± 1; CVF 0.1 ± 0.6; saline 1.7 ± 1.2). In lumbosacral nerve roots significantly less infiltrating ED1 positive macrophages and CD11bc (expressing complement receptor 3 or CR3) positive inflammatory cells were present in CVF treated EAN rats while there was a limited decrease in inflammation in the sCR1 treated animals compared to the saline treated rats (ED1: sCR1 1.4 ± 1.2; CVF 0.5 ± 0.6; saline 1.7 ± 1.2; CD11bc: sCR1 1.9 ± 1.2; CVF 0.9 ± 1; saline 2.1 ± 1.2). Our findings suggest that complement depletion by CVF is more effective than complement blockade by sCR1 in reducing the severity of inflammatory peripheral nerve demyelination.