川芎嗪对紫杉醇致神经病理性疼痛大鼠的疗效及其对坐骨神经中神经生长因子表达的影响

目的探讨川芎嗪对紫杉醇致神经病理性疼痛大鼠的疗效及其对坐骨神经中神经生长因子(NGF)表达的影响。方法成年雄性SD大鼠30只随机分为A组(对照组,n=6)、B组(n=8)、C组(n=8)、D组(n=8)。以首次给药为d1,实验前一日为d0,各组分别在d1、d3、d5、d7腹腔注入2.0 mg/(kg·d)紫杉醇。于d1~d14,B组腹腔注入川芎嗪200 mg/(kg·d),C组口服普瑞巴林3 mg/(kg·d),D组同时腹腔注射川芎嗪和口服普瑞巴林,剂量同B组、C组。分别于d0和d7、d12、d16、d20测定大鼠的机械缩足反射阈值(MWT)和热缩足潜伏期(TWL)。采用透射电镜观察各组大鼠坐骨神经的超微结构,用免疫组化法检测大鼠坐骨神经中NGF的表达。结果 4组大鼠d0时后肢MWT差异无统计学意义(均P0.05);D组大鼠d7~d20时后肢平均MWT与A组及C组相比明显升高(均P0.05);B、C组大鼠d12~d20时后肢MWT与A组相比明显升高(均P0.05);B组d12、d16时MWT明显高于C组(均P0.05)。4组大鼠d0时后肢TWL差异无统计学意义(均P0.05);B、C、D组大鼠d7~d20时后肢TWL与A组相比明显升高(均P0.05);D组大鼠d7~d20时后肢TWL与C组相比明显升高(均P0.05);C组大鼠d16、d20时后肢TWL与B组相比明显升高(均P0.05)。透射电镜下,A组大鼠的坐骨神经纤维髓鞘板层结构明显松散,呈网状,严重脱髓鞘;B组、C组、D组大鼠的坐骨神经纤维髓鞘板层结构较松散,明显脱髓鞘,但较A组明显减轻,且B组、D组脱髓鞘程度较C组更轻。与A组比较,B组和C组大鼠坐骨神经中NGF表达减少不明显(均P0.05),D组大鼠坐骨神经中NGF表达明显减少(P0.05)。结论川芎嗪能有效防治紫杉醇所致的大鼠神经病理性疼痛,疗效与普瑞巴林相似并有协同作用,作用机理可能是减低坐骨神经NGF的表达,减轻神经损伤。     

Cold intolerance and neuropathic pain after peripheral nerve injury in upper extremity

Cold intolerance and pain can be a substantial problem in patients with peripheral nerve injury. We aimed at investigating the relationships among sensory recovery, cold intolerance, and neuropathic pain in patients affected by upper limb peripheral nerve injury (Sunderland type V) treated with microsurgical repair, followed by early sensory re‐education. In a cross‐sectional clinical study, 100 patients (male/female 81/19; age 40.5 ± 14.8 years and follow‐up 17 ± 5 months, mean ± SD), with microsurgical nerve repair and reconstruction in the upper extremity and subsequent early sensory re‐education, were evaluated, using Cold Intolerance Symptoms Severity questionnaire‐Italian version (CISS‐it, cut‐off pathology >30/100 points), CISS questionnaire‐12 item version (CISS‐12, 0‐46 points‐grouping: healthy that means no cold intolerance [0‐14], mild [15‐24], moderate [25‐34], severe [35‐42], very severe [43‐46] cold intolerance), probability of neuropathic pain (DouleurNeuropathique‐4; [DN4] 4/10), deep and superficial sensibility, tactile threshold (monofilaments), and two‐point discrimination (cutoff S2; Medical Research Council scale for sensory function; [MRC‐scale]). A high CISS score is associated with possible neuropathic pain (DN4 ≥ 4). Both a low CISS‐it score (ie, < 30) and DN4 < 4 is associated with good sensory recovery (MRC ≥ 2). In conclusion patients affected by upper limb peripheral nerve injuries with higher CISS scores more often suffer from cold intolerance and neuropathic pain, and the better their sensory recovery is, the less likely they are to suffer from cold intolerance and neuropathic pain.     

Effects of local continuous release of brain derived neurotrophic factor (BDNF) on peripheral nerve regeneration in a rat model

The purpose of this study was to evaluate the effect of continuously released BDNF on peripheral nerve regeneration in a rat model. Initial in vitro evaluation of calcium alginate prolonged-release-capsules (PRC) proved a consistent release of BDNF for a minimum of 8 weeks. In vivo, a worst case scenario was created by surgical removal of a 20-mm section of the sciatic nerve of the rat. Twenty-four autologous fascia tubes were filled with calcium alginate spheres and sutured to the epineurium of both nerve ends. The animals were divided into 3 groups. In group 1, the fascial tube contained plain calcium alginate spheres. In groups 2 and 3, the fascial tube contained calcium alginate spheres with BDNF alone or BDNF stabilized with bovine serum albumin, respectively. The autocannibalization of the operated extremity was clinically assessed and documented in 12 additional rats. The regeneration was evaluated histologically at 4 weeks and 10 weeks in a blinded manner. The length of nerve fibers and the numbers of axons formed in the tube was measured. Over a 10-week period, axons have grown significantly faster in groups 2 and 3 with continuously released BDNF compared to the control. The rats treated with BDNF (groups 2 and 3) demonstrated significantly less autocannibalization than the control group (group 1). These results suggest that BDNF may not only stimulate faster peripheral nerve regeneration provided there is an ideal, biodegradable continuous delivery system but that it significantly reduces the neuropathic pain in the rat model.     

Variation in rat sciatic nerve anatomy: implications for a rat model of neuropathic pain

We discovered a variation of rat sciatic nerve anatomy as an incidental finding during the anatomical exploration of the nerve lesion site in a rat neuropathic pain model. To confirm the composition and distribution of rat sciatic nerve, macroscopic anatomical investigation was performed in both left and right sides in 24 adult Sprague-Dawley rats. In all rats, the L4 and L5 spinal nerves were fused tightly to form the sciatic nerve. However, the L6 spinal nerve did not fuse with this nerve completely as a part of the sciatic nerve, but rather sent a thin branch to it in 13 rats (54%), whereas in the remaining 11 rats (46%), L6 ran separately along with the sciatic nerve. Also, the L3 spinal nerve sent a thin branch to the L4 spinal nerve or sciatic nerve in 6 rats (25%). We conclude that the components of sciatic nerve in Sprague-Dawley rats vary from L3 to L6; however, the major components are L4 and L5 macroscopically. This finding is in contrast to the standard textbooks of rat anatomy which describe the sciatic nerve as having major contributions from L4, L5, and L6.     

Comparison of sildenafil,fluoxetine and its co-administration against chronic constriction injury induced neuropathic pain in rats: An influential additive effect

ABSTRACT

Current drug treatment available for neuropathic pain (NP) provides meager and partial pain relief due to incomplete efficacy and dose-dependent adverse effect. Hence, combination therapy can provide prolongation in analgesic effect with milder side effects. The present investigation aimed at observing the effects of sildenafil (SD) on Fluoxetine (FLX) in attenuation of chronic constriction injury (CCI) induced NP in rats. CCI was achieved in rats by placing four loose ligations around the sciatic nerve and rats were received respective treatments on SD and FLX till 14 days further behaviors parameters like heat hyperalgesia and allodynia, pin prick and acetone drop test were executed in order to access thermal, mechanical and cold allodynia, respectively, on a predetermined time interval. On the 21st day the animals were sacrificed for determination of total protein, myeloperoxidase activity in the adjoining muscular tissues while glutathione and TNF-α in the sciatic nerve. Co-administration of SD + FLX + CCI gave the pronounced effect that was superior over individual responses of SD and FLX in all behavioral as well as biochemical parameters. It was observed that attenuation in the altered behavioral pattern of CCI induced rats was modified prominently from 3rd day only in a group of rats treated with SD + FLX + CCI. The whole study was finally supported by histopathological results. Finally, it was concluded that SD produces an additive effect when given with FLX in attenuation of NP may be due to elevation in the level of intracellular concentrations of cyclic guanosine monophosphate which further causes downregulation of calcium channel.     

单一腰6脊神经根结扎延长大鼠神经病理性疼痛发展期的研究

目的：腰5和腰6脊神经根共同结扎是目前最常见的神经病理性疼痛鼠模型,但结扎后大鼠的机械触诱发痛会在24～72 h内迅速发展,时间窗过短,本课题组探索和研究了一种新型的神经病理性疼痛大鼠模型—单一腰6脊神经根结扎鼠模型。方法将36只大鼠随机分为空白对照组、腰5和腰6脊神经根结扎组、单一腰6脊神经根结扎组及假手术组,除单一腰6脊神经根结扎组18只外,其余3组每组6只大鼠;分别检测其50％机械缩爪阈值（50％PWT）。另取54只大鼠,随机分为空白对照组、腰5和腰6脊神经根结扎组、腰6脊神经根结扎组,各组大鼠只数分别为6只、24只、24只。采用蛋白免疫印迹法检测脊髓背角胶质纤丝酸性蛋白（ GFAP）在结扎术后第1 d、第7 d、第14 d和第28 d的表达。结果单一腰6脊神经根结扎组产生了长期发展的机械触诱发痛（1～14 d）;且大鼠同侧脊髓背角GFAP表达随之升高。结论单一腰6脊神经根结扎鼠模型可以作为研究神经病理性疼痛发展期具体机制的有效模型。     

Effects of nitric oxide on the prefrontal cortex in stressed rats

BACKGROUND:Nitric oxide(NO)exhibits both protective and detrimental effects in the central nervous system.OBJECTIVE:To investigate the effect of NO on the prefrontal codex in neonatal stressed rats.DESIGN,TIME AND SETTING:A randomized,controlled,animal study was performed at the Anatomical Department of Iran University of Medical Sciences from May 2007 to August 2008.MATERIALS:Forty-eight male,Wistar rats were obtained from Pasteur's Institute,Tehran,Iran.METHODS:Rat stress models were established by immobilization and randomly received intraperitoneal injection of 2 mL physiological saline,L-arginine(200 mg/kg)as a NO precursor,N(G)-nitro-L-arginine methyl ester(20 mg/kg),or subcutaneous injection of 7-nitroindazole(25 mg/kg)as a NO synthase inhibitor.MAIN OUTCOME MEASURES:After the rats were treated for 4 weeks,the frontal codex was harvested for histological observation and NO detection.RESULTS:Subcutaneous administration of N(G)-nitro-L-arginine methyl ester or 7-nitroindazole resulted in significantly lower prefrontal cortex thickness and NO production compared with subcutaneous administration of L-arginine(P < 0.05).Prefrontal cortex thickness significantly increased in rats following L-arginine treatment,compared with physiological saline intervention(P< 0.05).CONCLUSION:NO exhibited protective effects on the prefrontal codex of stressed rats.     

吗啡成瘾和正常大鼠前额叶皮质表达的蛋白质组学变化

The prefrontal cortex is involved in the regulation and control of substance addiction-related cognitive,behavioral,and emotional changes.The present study identified prefrontal cortex protein profiles in morphine-addicted rats;these were subsequently compared with normal rats.Results showed 87 protein spots with differentially expressed levels in the morphine addiction group,with the majority located in meta acid zones at pH 4.2-6.8 and having a molecular weight of 30-110 kDa.In addition,2 protein spots were identified as being associated with neurotoxicity(Snap25 isoform β-Snap25 of synaptosomal-associated protein 25 and β-actin).     

Ibotenic acid lesions of the medial prefrontal cortex block the development and expression of 3,4-methylenedioxymethamphetamine-induced behavioral sensitization in rats

There is ample evidence that plastic changes in the nervous system require the excitatory amino acid transmission. This appears to be also the case for psychostimulant-induced behavioral sensitization. More specifically the glutamatergic input from the medial prefrontal cortex (mPFC) to the VTA and the NAc appears to be involved in behavioral sensitization processes. However, dissociations regarding the role of the mPFC with respect to the development and expression of sensitization, as well as with respect to the psychostimulant being studied (amphetamine versus cocaine) appear to exist. The present study examined the role of the dorsal mPFC in the development and expression of 3,4-methylenedioxymethamphetamine (MDMA)-induced sensitization. Bilateral ibotenic acid or sham lesions of the dorsal mPFC were performed 7 days prior to or 4 days after a context-dependent sensitization-inducing regimen of MDMA (15 mg/kg i.p.) or saline. Rats were then challenged with MDMA (5 mg/kg i.p.) after 12 days of withdrawal. Ibotenic acid lesions did not affect the activating effects of MDMA, but prevented the development and expression of MDMA sensitization. Thus, the distance traveled during the development phase of sensitization increased in sham-lesioned rats but not in ibotenic-lesioned animals. Similarly, sham-lesioned rats showed a sensitized response when challenged with MDMA after the withdrawal period, an effect not observed in ibotenic-lesioned animals. These data reinforce the view that the dorsal mPFC is involved in psychostimulant sensitization and more specifically they indicate that the dorsal mPFC plays a key role in the development and expression of MDMA-induced behavioral sensitization.     

Unilaterally activated systems in rats self-stimulating at sites in the medial forebrain bundle, medial prefrontal cortex, or locus coeruleus

Rats with electrodes in either the posterior medial forebrain bundle (MFB), the anterior MFB, the medial prefrontal cortex, or the locus coeruleus self-stimulated during a 45 min period following the injection of [14C]2-deoxyglucose. They were then sacrificed and their brains prepared for autoradiography. The autoradiographs were analyzed for unilaterally activated neural systems, using a computerized image analyzing system to compare the darkness of neural structures on the stimulated side with the darkness of the same structures on the unstimulated side. There was extensive overlap in the neural structures unilaterally activated by stimulation in the anterior and posterior MFB; but there was no overlap between the structures activated by MFB stimulation and the structures activated by stimulation at either of the extradiencephalic sites; nor did the forebrain, diencephalic, and midbrain sites have any readily apparent bilateral effects in common. If there is a substrate common to MFB self-stimulation and extradiencephalic self-stimulation, its activation is not revealed by 2-deoxyglucose autoradiography.     

Effects of acute and chronic clozapine on dopaminergic function in medial prefrontal cortex of awake, freely moving rats

We previously showed that chronic administration of the clinically atypical and clinically superior antipsychotic drug clozapine selectively reduces dopamine (DA) release in the nucleus accumbens but not neostriatum, and that this effect appears mediated by anatomically selective mesolimbic DA depolarization blockade. The present study extends that research to another mesocorticolimbic DA locus, the medial prefrontal cortex. Acute clozapine challenge (5-40 mg/kg i.p.) produced dose-dependent increased extracellular levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the medial prefrontal cortex of awake, free-moving rats as measured by in vivo brain microdialysis. Chronic clozapine treatment (20 mg/kg/day for 21 days) did not significantly change basal extracellular levels of DA, DOPAC or HVA. Acute clozapine challenge on day 22 in the chronic clozapine-treated animals produced no significant differences in medial prefrontal cortex DA, DOPAC or HVA as compared to chronic vehicle-treated animals, indicating that tolerance to clozapine does not develop in the mesocortical DA system, in contrast to the mesolimbic system. The DA agonist apomorphine (100 micrograms/kg) produced decreased basal extracellular levels of DA, DOPAC and HVA in medial prefrontal cortex of both chronic clozapine-treated and chronic vehicle-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Agmatine promotes expression of brain-derived neurotrophic factor in brainstem facial nucleus in the rat facial nerve injury model★

BACKGROUND: Studies have shown that agmatine can reduce inhibition of neuronal regeneration by increasing cyclic adenosine monophosphate and brain-derived neurotrophic factor (BDNF) in the hippocampus of morphine-dependent rats. The hypothesis that agmatine exerts similar effects on facial nerve injury deserves further analysis.OBJECTIVE: To study the effects of peritoneal agmatine injection on BDNF levels in the rat brainstem after facial nerve injury.DESIGN, TIME AND SETTING: A controlled animal experiment was performed at the Department of Otolaryngology-Head and Neck Surgery at the Second Affiliated Hospital, Chongqing University of Medical Sciences (Chongqing, China), between October and December in 2007.MATERIALS: Twenty-four male Sprague-Dawley rats were randomly divided into a control, a lesion, and an agmatine treatment group, with eight rats in each group. Bilateral facial nerve anastomosis was induced in the lesion and agmatine treatment groups, while the control group remained untreated. A rat BDNF Enzyme-linked immunosorbent assay kit was used to measure BDNF levels in the brainstem facial nucleus.METHODS: Starting on the day of lesion, the agmatine group received a peritoneal injection of 100 mg/kg agmatine, once per day, for a week, whereas rats in the lesion group received saline injections.MAIN OUTCOME MEASURES: BDNF levels in the brainstem containing facial nucleus were measured by ELISA.RESULTS: Twenty-four rats were included in the final analysis without any loss. Two weeks after lesion, BDNF levels were significantly higher in the lesion group than in the control group (P<0.01). A significant increase was noted in the agmatine group compared to the lesion group (P<0.01).CONCLUSION: Agmatine can substantially increase BDNF levels in the rat brainstem after facial nerve injury.     

脊神经结扎神经痛大鼠脊髓背角广动力范围神经元的电生理学特性(英文)

目的探讨腰5脊神经结扎(spinal nerve ligation, SNL)后,大鼠脊髓背角的广动力范围(wide dynamic range,WDR)神经元电生理学特性的改变。方法将健康雄性 Sprague-Dawley 大鼠分为正常组和 SNL 组,利用细胞外电生理学方法记录脊髓背角的 WDR 神经元放电。结果与正常大鼠相比,SNL 组大鼠 WDR 神经元兴奋性增加,表现为感受野扩大、有自发放电的神经元比例增加,以及 C 纤维诱发放电的阈值降低、潜伏期缩短、发放时程增加。此外,SNL组大鼠WDR神经元A和C纤维诱发放电数目较正常大鼠降低。结论大鼠腰5脊神经结扎后主要引起WDR神经元的兴奋性增加。WDR神经元的兴奋性增加可能参与神经病理痛的发生。     

Effects of cyclooxygenase 2 inhibitor on growth-associated protein 43 and nerve growth factor expression in dorsal root ganglion during neuropathic pain development

BACKGROUND： Inflammatory responses in injured nerves have been recognized as important factors for initially sensitizing nociceptive neurons. Cyclooxygenase （COX） is the rate-limiting enzyme in prostaglandin synthesis, and COX-2 inhibitor is involved in mechanisms of analgesia and anti-inflammation. OBJECTIVE： To investigate the effects of COX-2 inhibitor on thermal and mechanical hyperalgesia, as well as expression of growth associated protein 43 （GAP-43） and nerve growth factor （NGF） in dorsal root ganglion, in a rat model of neuropathic pain due to chronic constriction injury. DESIGN, TIME AND SETTING： A randomized, controlled, comparison study that was performed at the Surgical Department and Pathological Laboratory, Second Affiliated Hospital of Shantou University Medical College from September 2006 to September 2007. MATERIALS： COX-2 inhibitor, Iornoxicam, was purchased from Nycomed Pharmaceutical （Austria）; rabbit anti-GAP-43, and rabbit anti-NGF polyclonal antibodies were purchased from Boster, Wuhan, China. METHODS： A total of 50 adult, Wistar rats were randomly assigned to four groups： normal control （n = 5）, model （n = 15）, normal saline control （n = 15）, and Iornoxicam treatment （n =15）. With exception of the control group, the sciatic nerve of all rats was loosely ligated to establish a model of chronic constriction injury. The model rats were divided into three subgroups according to varying post-operative survival periods： 3, 7 and 14 days （n = 5）, respectively. Rats in the Iornoxicam treatment group were intraperitoneally injected with 1.3 mg/kg lornoxicam every 12 hours throughout the entire experimental procedure. Rats in the normal saline control group were intraperitoneally injected with 1.3 mL/kg saline. MAIN OUTCOME MEASURES： Immunohistochemistry revealed expression of GAP-43 and NGF in the L5 dorsal root ganglions. Mechanical withdrawal threshold and thermal withdrawal latency were used to observe neurological behavioral changes in rats. RESULTS： The relative gray values of GAP-43- and NGF-positive neurons in the model group were remarkably increased compared with the normal control rats （P 〈 0.01）, while the relative gray values in the Iomoxicam treatment group were significantly less than the model and normal saline control groups （P 〈 0.01）. Mechanical withdrawal threshold and thermal withdrawal latency gradually decreased with increasing injury time in the model, normal saline control, and Iornoxicam treatment groups, and were significantly less than the normal control group （P 〈 0.05）. In addition, mechanical withdrawal threshold and thermal withdrawal latency were significantly greater in the Iornoxicam treatment group compared with the model and normal saline control groups （P 〈 0.05）. CONCLUSION： Intraperitoneal injection of the COX-2 inhibitor Iornoxicam attenuated mechanical and thermal hyperalgesia induced by sciatic nerve chronic constriction injury and inhibited the increased expression of GAP-43 and NGF.     

Effects of continuous peripheral nerve block by tetrodotoxin on growth associated protein-43 expression during neuropathic pain development

BACKGROUND: Peripheral nerve injury may lead to neuropathic pain and cause a markedly increase expression of growth associated protein-43 (GAP-43) in the spinal cord and dorsal root ganglion, local anesthetics blocking electrical impulse propagation of nerve fibers may also affect the expression of GAP-43 in the spinal cord and dorsal root ganglion. OBJECTIVE: To determine the effects of continuous peripheral nerve block by tetrodotoxin before and after nerve injury on GAP-43 expression in the dorsal root ganglion during the development of neuropathic pain. DESIGN: A randomized controlled animal experiment. SETTINGS: Department of Anesthesiology, the Second Hospital of Xiamen City; Department of Anesthesiology, the Second Affiliated Hospital of Shantou University Medical College. MATERIALS: Thirty-five Sprague Dawley (SD) rats, weighing 200–250 g, were randomly divided into four groups: control group (n =5), simple sciatic nerve transection group (n =10), peripheral nerve block before and after sciatic nerve transection groups (n =10). All the sciatic nerve transection groups were divided into two subgroups according to the different postoperative survival periods: 3 and 7 days (n =5) respectively. Mouse anti-GAP-43 monoclonal antibody (Sigma Co., Ltd.), supervision TM anti-mouse reagent (HRP, Changdao antibody diagnosis reagent Co., Ltd., Shanghai), and HMIAS-100 image analysis system (Qianping Image Engineering Company, Tongji Medical University) were employed in this study. METHODS: This experiment was carried out in the Department of Surgery and Pathological Laboratory, the Second Affiliated Hospital of Shantou University Medical College from April 2005 to April 2006. ①The animals were anesthetized and the right sciatic nerve was exposed and transected at 1 cm distal to sciatic notch. ② Tetrodotoxin 10 μg/kg was injected percutaneously between the greater trochanter and the posterior superior iliac spine of right hind limb to block the sciatic nerve proximally at 1 hour before or 4 hours after nerve injury respectively, the injection was repeated in all the rats every 12 hours. ③ At 3 or 7 days after nerve injury, immunohistochemistry and image analysis were used to evaluate the expression of GAP-43 in the dorsal root ganglions of L5 to the transected sciatic nerve, and quantitative analysis was also performed. ④ Statistical analysis was performed using one way analysis of variance followed by t test. MAIN OUTCOME MEASURE: Expression of GAP-43 in the right dorsal root ganglions of L5. RESULTS: All the 35 SD rats were involved in the final analysis of results. In normal rats, there were very low expressions of GAP-43 in the dorsal root ganglions. In simple sciatic nerve transection rats 3 and 7 days after sciatic nerve transection, the average absorbance value of GAP-43 immunopositive neurons were significantly different from that in normal rats (t =8.806, 6.771, P < 0.01). Whereas 3 and 7 days after sciatic nerve transection in rats with peripheral nerve block before and after nerve injury, the average absorbance value of GAP-43 immunopositive neurons were not significantly different from that in normal rats (P > 0.05). CONCLUSION: Local anesthetic continuous peripheral nerve block before or after nerve injury can suppress nerve injury induced high expression of GAP-43 during the development of neuropathic pain.     

A subpopulation of rats show social and sleep-waking changes typical of chronic neuropathic pain following peripheral nerve injury

Neuropathic conditions for which treatment is sought, the so-called chronic pain syndrome, are characterized usually by complex behavioural disturbances as well as pain. In this study we evaluated whether social behavioural and sleep disruptions occurred after nerve injury. Before and after chronic constriction of the sciatic nerve, resident-intruder and sleep-wake cycles, as well as mechanical and thermal allodynia/hyperalgesia, were quantified. Sciatic nerve injury in all animals reduced withdrawal thresholds to tactile and thermal (cold) stimuli. Resident-intruder and sleep-waking behaviours were altered in some but not all animals. One group (30%, 'persistent change') had enduring reductions in dominant behaviour to an intruder and decreased slow-wave sleep and increased wakefulness during both light and dark cycles. Another group (25%, 'recovery') had a transient reduction in dominant behaviours and decreased slow-wave sleep and increased wakefulness during only the light cycle. In a third group (45%, 'no effect') resident-intruder and sleep-waking behaviours remained normal. Our finding that the degree of 'pain' as inferred from the allodynia/hyperalgesia was identical in all animals suggests that the alterations to resident-intruder and sleep-wake cycles were independent of the level of sensory disturbance. An absence of correlation between intensity of sensory disturbances and measures of disability (loss of sleep, familial/social problems) is also characteristic of human neuropathic pain. These data indicate that: (i) in a subpopulation of animals sciatic injury results in two of the major complex behavioural changes which are characteristic of neuropathic pain in humans; (ii) testing only for allodynia and hyperalgesia is not sufficient to detect this subpopulation.     

CRF receptor antagonist attenuates stress-induced noradrenaline release in the medial prefrontal cortex of rats

Noradrenaline release in rat medial prefrontal cortex (PFC) was measured using a brain microdialysis technique. Immobilization stress increased noradrenaline release to a maximum level of 248.7 ± 12.8% of the basal release, which was significantly attenuated by preinjection of α-helical CRF_9–41 (50 μg/rat) into the lateral cerebroventricle. Intracerebroventricular injection of CRF also increased noradrenaline release in the medial PFC. These results suggest that immobilization-stress facilitates noradrenaline release in the medial PFC through activation of the CRF system in the brain.     

Brain-derived neurotrophic factor applied to the motor cortex promotes sprouting of corticospinal fibers but not regeneration into a peripheral nerve transplant

Previous experiments from our laboratory have shown that application of brain-derived neurotrophic factor (BDNF) to the red nucleus or the motor cortex stimulates an increase in the expression of regeneration-associated genes in rubrospinal and corticospinal neurons. Furthermore, we have previously shown that BDNF application stimulates regeneration of rubrospinal axons into a peripheral graft after a thoracic injury. The current study investigates whether application of BDNF to the motor cortex will facilitate regeneration of corticospinal neurons into a peripheral nerve graft placed into the thoracic spinal cord. In adult Sprague Dawley rats, the dorsal columns and the corticospinal tract between T9 and T10 were ablated by suction, and a 5-mm-long segment of predegenerated tibial nerve was autograft implanted into the lesion. With an osmotic pump, BDNF was infused directly into the parenchyma of the motor cortex for 14 days. Growth of the corticospinal tract into the nerve graft was then evaluated by transport of an anterograde tracer. Anterogradely labeled corticospinal fibers were not observed in the peripheral nerve graft in animals treated with saline or BDNF. Serotinergic and noradrenergic fibers, as well as peripheral sensory afferents, were observed to penetrate the graft, indicating the viability of the peripheral nerve graft as a permissive growth substrate for these specific fiber types. Although treatment of the corticospinal fibers with BDNF failed to produce regeneration into the graft, there was a distinct increase in the number of axonal sprouts rostral to the injury site. This indicates that treatment of corticospinal neurons with neurotrophins, e.g., BDNF, can be used to enhance sprouting of corticospinal axons within the spinal cord. Whether such sprouting leads to functional recovery after spinal cord injury is currently under investigation.     

Traumatic peripheral nerve injuries: epidemiological findings,neuropathic pain and quality of life in 158 patients

The objectives of this study were (1) epidemiological analysis of traumatic peripheral nerve injuries; (2) assessment of neuropathic pain and quality of life in patients affected by traumatic neuropathies. All consecutive patients with a diagnosis of traumatic neuropathies from four Italian centres were enrolled. Electromyography confirmed clinical level and site diagnosis of peripheral nerve injury. All patients were evaluated by disability scales, pain screening tools, and quality of life tests. 158 consecutive patients for a total of 211 traumatic neuropathies were analysed. The brachial plexus was a frequent site of traumatic injury (36%) and the radial, ulnar, and peroneal were the most commonly involved nerves with 15% of iatrogenic injuries. Seventy‐two percent of the traumatic neuropathies were painful. Pain was present in 66% and neuropathic pain in 50% of all patients. Patients had worse quality of life scores than did the healthy Italian population. Moreover, there was a strong correlation between the quality of life and the severity of the pain, particularly neuropathic pain (Short Form‐36 [SF‐36] p < 0.005; Beck Depression Inventory [BDI] p < 0.0001). Traumatic neuropathies were more frequent in young males after road accidents, mainly in the upper limbs. Severe neuropathic pain and not only disability contributed to worsening the quality of life in patients with traumatic neuropathies.