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1.
Rodrigues-Filho R Campos MM Ferreira J Santos AR Bertelli JA Calixto JB 《Brain research》2004,1018(2):159-170
Recently, our laboratory has proposed the avulsion of rat brachial plexus as a new and reliable model for the study of neuropathic pain. In this model, the neuropathy can be detected even at distant sites from the injury, both in ipsilateral and contralateral hindpaws. The purpose of this study was to pharmacologically characterise this behavioural model of persistent peripheral neuropathic pain by assessing the effects of several analgesic drugs currently used in clinical practice. For this purpose, the effects of these drugs on the mechanical and cold allodynia were analysed 20-40 days after rat brachial plexus avulsion. Injection of saline, administered by the same route as the other drugs, did not significantly affect the nociceptive threshold either in sham-operated or in neuropathic rats. However, administration of the opioid analgesic morphine (5 mg/kg, s.c.), the alpha2 adrenoceptor agonist clonidine (300 microg/kg, i.p.), the NMDA receptor antagonist ketamine (25 mg/kg, i.p.) or the anticonvulsant drug gabapentin (70 mg/kg, p.o.) consistently reduced both mechanical and cold allodynia following avulsion of rat brachial plexus. The administration of the selective COX-2 inhibitor celecoxib (10 mg/kg, p.o.) blocked mechanical allodynia, but not cold allodynia, whereas the sodium channel blocker lidocaine (40 mg/kg, i.p.) attenuated only cold allodynia. The non-steroidal anti-inflammatory drug diclofenac (100 mg/kg, i.p.), the steroidal anti-inflammatory dexamethasone (1.5 mg/kg, i.p.) and the antidepressant imipramine (10 mg/kg, i.p.) all failed to significantly attenuate both mechanical and cold allodynia in the rats following avulsion of brachial plexus. These findings suggest that avulsion-associated mechanical and cold allodynia, two classic signs of persistent neuropathic pain, were consistently prevented by several analgesics currently available in clinical practice, namely morphine, clonidine, ketamine and gabapentin, and to a lesser extent by celecoxib and lidocaine. Therefore, this new proposed model of persistent nociception seems to be suitable for the study of the underlying mechanisms involved in neuropathic pain and for the identification of potential clinically relevant drugs to treat this aspect of peripheral neuropathy. 相似文献
2.
Electroacupuncture has traditionally been used to treat pain, but its effect on pain following brachial plexus injury is still unknown. In this study, rat models of an avulsion injury to the left brachial plexus root(associated with upper-limb chronic neuropathic pain) were given electroacupuncture stimulation at bilateral Quchi(LI11), Hegu(LI04), Zusanli(ST36) and Yanglingquan(GB34). After electroacupuncture therapy, chronic neuropathic pain in the rats' upper limbs was significantly attenuated. Immunofluorescence staining showed that the expression of β-endorphins in the arcuate nucleus was significantly increased after therapy. Thus, experimental findings indicate that electroacupuncture can attenuate neuropathic pain after brachial plexus injury through upregulating β-endorphin expression. 相似文献
3.
SYM-2081 a kainate receptor antagonist reduces allodynia and hyperalgesia in a freeze injury model of neuropathic pain 总被引:1,自引:0,他引:1
Cold-freeze injury at -4 degrees C to the rat sciatic nerve produces mechanical allodynia and thermal hyperalgesia [M.A. Kleive, P.S. Jungbluth, J.A. Uhlenkamp, K.C. Kajander, Cold injury to rat sciatic nerve induces thermal hyperalgesia or analgesia, 8th World Congress on Pain, Vancouver, BC, Canada, August 1996 (Abstract).]. The NMDA receptor, an excitatory amino acid (EAA) receptor, appears to be involved in the development of allodynia and hyperalgesia following nerve injury. The role, if any, of the kainate receptor, another EAA receptor, remains unknown. In the current study, we evaluated whether (2S,4R)-4-methylglutamic acid (SYM-2081), a recently developed kainate receptor antagonist, attenuates increased responsiveness following cold injury to the sciatic nerve. During baseline testing, Sprague-Dawley rats were evaluated for frequency of withdrawal from von Frey filaments and latency of withdrawal from a radiant thermal source. Animals were then anesthetized, the left sciatic nerve was exposed, and the nerve was cooled to -4 degrees C for 15 min (n=24). For control rats (n=24), all procedures were identical except that the nerve was maintained at 37 degrees C. Testing resumed on the third day following surgery. On the fifth post-operative day, SYM-2081 (150 or 100 mg/kg), fentanyl citrate (0. 04 mg/kg) or vehicle was injected intraperitoneally. Injury to the rat sciatic nerve induced a significant increase in withdrawal frequency and a significant decrease in withdrawal latency (ANOVA, p<0.05). SYM-2081 and fentanyl significantly reduced these responses (p<0.05). These results suggest that kainate and opioid receptors are involved in the mechanical allodynia and thermal hyperalgesia that develop following cold injury to the sciatic nerve. 相似文献
4.
Effects of electroacupuncture on cold allodynia in a rat model of neuropathic pain: mediation by spinal adrenergic and serotonergic receptors 总被引:6,自引:0,他引:6
Kim SK Park JH Bae SJ Kim JH Hwang BG Min BI Park DS Na HS 《Experimental neurology》2005,195(2):51-436
The present study was performed to examine the effects of electroacupuncture (EA) on cold allodynia and its mechanisms related to the spinal adrenergic and serotonergic systems in a rat model of neuropathic pain. For the neuropathic surgery, the right superior caudal trunk was resected at the level between S1 and S2 spinal nerves innervating the tail. Two weeks after the nerve injury, EA stimulation (2 or 100 Hz) was delivered to Zusanli (ST36) for 30 min. The behavioral signs of cold allodynia were evaluated by the tail immersion test [i.e., immersing the tail in cold water (4 degrees C) and measuring the latency to an abrupt tail movement] before and after the stimulation. And then, we examined the effects of intrathecal injection of prazosin (alpha1-adrenoceptor antagonist, 30 microg), yohimbine (alpha2-adrenoceptor antagonist, 30 microg), NAN-190 (5-HT1A antagonist, 15 microg), ketanserin (5-HT2A antagonist, 30 microg), and MDL-72222 (5-HT3 antagonist, 12 microg) on the action of EA stimulation. Although both 2 Hz and 100 Hz EA significantly relieved the cold allodynia signs, 2 Hz EA induced more robust effects than 100 Hz EA. In addition, intrathecal injection of yohimbine, NAN-190, and MDL-72222, but not prazosin and ketanserin, significantly blocked the relieving effects of 2 Hz EA on cold allodynia. These results suggest that low-frequency (2 Hz) EA is more suitable for the treatment of cold allodynia than high-frequency (100 Hz) EA, and spinal alpha2-adrenergic, 5-HT1A and 5-HT3, but not alpha1-adrenergic and 5-HT2A, receptors play important roles in mediating the relieving effects of 2 Hz EA on cold allodynia in neuropathic rats. 相似文献
5.
Spinal cord injury (SCI) elicits chronic pain in 65% of individuals. In addition, SCI afflicts an increasing number of aged individuals, and those with SCI are predisposed to shorter lifespan. Our group previously identified that deletion of the microRNA miR-155 reduced neuroinflammation and locomotor deficits after SCI. Here, we hypothesized that aged mice would be more susceptible to pain symptoms and death soon after SCI, and that miR-155 deletion would reduce pain symptoms in adult and aged mice and improve survival. Adult (2 month-old) and aged (20 month-old) female wildtype (WT) and miR-155 knockout (KO) mice received T9 contusion SCI. Aged WT mice displayed reduced survival and increased autotomy – a symptom of spontaneous pain. In contrast, aged miR-155 KO mice after SCI were less susceptible to death or spontaneous pain. Evoked pain symptoms were tested using heat (Hargreaves test) and mechanical (von Frey) stimuli. At baseline, aged mice showed heightened heat sensitivity. After SCI, adult and aged WT and miR-155 KO mice all exhibited heat and mechanical hypersensitivity at all timepoints. miR-155 deletion in adult (but not aged) mice reduced mechanical hypersensitivity at 7 and 14 d post-SCI. Therefore, aging predisposes mice to SCI-elicited spontaneous pain and expedited mortality. miR-155 deletion in adult mice reduces evoked pain symptoms, and miR-155 deletion in aged mice reduces spontaneous pain and expedited mortality post-SCI. This study highlights the importance of studying geriatric models of SCI, and that inflammatory mediators such as miR-155 are promising targets after SCI for improving pain relief and longevity. 相似文献
6.
Introduction: End‐to‐side neurotization is currently used to treat brachial plexus injury, but it is not clear which donor nerve yields the best outcome. We performed experiments to determine the optimal donor nerve. Methods: A total of 66 male Sprague‐Dawley rats were assigned to 1 of 3 groups. Group A was the control group. In Group B, the phrenic nerve was used as the donor, while the ipsilateral C7 nerve root served as the donor in Group C. The epineurial window was used in end‐to‐side neurorrhaphy. Behavioral observations, histology, electrophysiology, and fluorescence retrotracing were performed postoperatively. Results: Fluorescence retrotracing confirmed nerve regeneration in both Groups B and C upon end‐to‐side neurotization. The outcome of Group B was superior to that of Group C. Conclusions: Use of the phrenic nerve as the donor nerve yielded a better outcome than use of the ipsilateral C7 nerve root. Muscle Nerve 50 : 67–72, 2014 相似文献
7.
目的探讨脊髓背根入髓区(DREZ)毁损术治疗臂丛神经损伤后神经病理性疼痛的疗效及其影响因素。方法回顾性分析2005年8月至2018年1月首都医科大学宣武医院功能神经外科收治的105例臂丛神经损伤后神经病理性疼痛患者的临床资料。根据患者疼痛及感觉缺失区对应的皮节,采用颈髓DREZ毁损术治疗。术后对所有患者行电话或门诊随访,随访内容为疼痛数字评分(NRS),以疼痛改善率[(术前NRS-术后NRS)/术前NRS×100%]评估患者疗效;其中改善率>75%为优秀,50%~75%为良好,≤50%为差。进一步采用单因素和多因素logistic回归分析法判断影响患者疗效的临床因素。结果105例患者的手术均成功。术后并发生症包括:手术同侧下肢麻木33例(31.4%)、下肢深感觉障碍20例(19.0%)、下肢无力9例(8.6%),手术对侧肢体麻木5例(4.8%),硬脊膜漏1例(1.0%);无一例出现切口愈合不良和感染。105例患者的随访时间为(47.3±25.5)个月(10~144个月)。至末次随访,105例患者疼痛的中位改善率(上、下四分位数)为100%(60%,100%);其中,74例(70.5%)为优秀,9例(8.6%)为良好,22例(20.9%)为差。单因素分析结果显示,性别、年龄、损伤原因、疼痛出现的时间、疼痛形式、性质及术后并发症对患者的疗效均无影响(均P>0.05),而病程和脊髓萎缩程度对疗效有影响(均P<0.05)。进一步多因素logistic回归分析结果显示,轻度脊髓萎缩是影响患者疗效的独立保护因素(OR=95.952,95%CI:4.171~2207.414,P=0.004)。结论DREZ毁损术治疗臂丛神经损伤后神经病理性疼痛疗效较好且多较持久;同时有轻度脊髓萎缩的患者手术疗效较好。 相似文献
8.
The relieving effects of electroacupuncture (EA) on mechanical allodynia and its mechanism related to the spinal opioid system were investigated in a rat model of neuropathic pain. To produce neuropathic pain in the tail, the right superior caudal trunk was resected between the S1 and S2 spinal nerves. Two weeks after the surgery, EA stimulation (2 or 100 Hz, 0.3 ms, 0.2-0.3 mA) was delivered to Zusanli (ST36) for 30 min. The degree of mechanical allodynia was evaluated quantitatively by touching the tail with von Frey hair (2.0 g) at 10 min intervals. These rats were then subjected to an i.t. injection with one of the three specific opioid agonists in successive ways: the mu agonist (DAMGO 25, 50 and 100 pmol), the delta agonist (DADELT II 0.5, 1 and 2 nmol), and the kappa agonist (U50488H 5, 10 and 20 nmol) separated by 10 min in cumulative doses. During 30 min of EA stimulation, specific opioid antagonists were subjected to i.t. injection: the mu antagonist (beta-FNA 5, 10 and 20 nmol), the delta antagonist (naltrindole 5, 10 and 20 nmol), and the kappa antagonist (nor-BNI 3, 6 and 12 nmol) separated by 10 min in cumulative doses. As a result, EA reduced the behavioral signs of mechanical allodynia. Two Hz EA induced a robust and longer lasting effect than 100 Hz. All three opioid agonists also showed relieving effects on mechanical allodynia. However, nor-BNI could not block the EA effects on mechanical allodynia, whereas beta-FNA or naltrindole significantly blocked EA effects. These results suggest that the mu and delta, but not kappa, opioid receptors in the spinal cord of the rat, play important roles in mediating relieving effects on mechanical allodynia induced by 2 Hz EA. 相似文献
9.
Grace PM Hutchinson MR Bishop A Somogyi AA Mayrhofer G Rolan PE 《Brain, behavior, and immunity》2011,25(3):503-513
Recent evidence demonstrates that peripheral immune cells contribute to the nociceptive hypersensitivity associated with neuropathic pain by infiltrating the central nervous system (CNS). We have recently developed a rat model of graded chronic constriction injury (CCI) by varying the exposure of the sciatic nerve and control non-nerve tissue to surgical placement of chromic gut. We demonstrate that splenocytes can contribute significantly to CCI-induced allodynia, as adoptive transfer of these cells from high pain donors to low pain recipients potentiates allodynia (P < 0.001). The phenomenon was replicated with peripheral blood mononuclear cells (P < 0.001). Adoptive transfer of allodynia was not achieved in sham recipients, indicating that peripheral immune cells are only capable of potentiating existing allodynia, rather than establishing allodynia. As adoptively transferred cells were found by flow cytometry to migrate to the spleen (P < 0.05) and potentiation of allodynia was prevented in splenectomised low pain recipients, adoptive transfer of high pain splenocytes may induce the migration of host-derived immune cells from the spleen to the CNS as observed by flow cytometry (P < 0.05). Importantly, intrathecal transfer of CD45+ cells prepared from spinal cords of high pain donors into low pain recipients led to potentiated allodynia (P < 0.001), confirming that infiltrating immune cells are not passive bystanders, but actively contribute to nociceptive hypersensitivity in the lumbar spinal cord. 相似文献
10.
脊髓背根入髓区毁损术治疗臂丛神经撕脱伤后疼痛 总被引:1,自引:0,他引:1
目的 探讨脊髓背根入髓区毁损术治疗臂丛神经撕脱伤后疼痛的疗效及安全性.方法 15例臂丛神经撕脱伤后疼痛患者接受脊髓背根入髓区毁损术治疗.分别于术后2周、6个月和1年采用视觉模拟评分(VAS)、汉密尔顿抑郁(HAMD)和焦虑评分(HAMA)来评估手术疗效.结果 手术早期,100%的患者疗效满意,经过1年的随访,疗效满意率逐渐下降.但是比较术后2周和术后6个月,以及比较术后2周和术后1年的VAS评分,结果 显示无统计学差异.并发症主要包括同侧下肢的轻度无力(3例)和同侧下肢深感觉障碍(3例),在术后6个月都有不同程度的恢复.结论 脊髓背根入髓区毁损术是治疗臂丛神经撕脱伤后疼痛的一种安全、有效的措施. 相似文献
11.
Francesca Madiai Virginia M. Goettl Syed-Rehan Hussain Alec R. Clairmont Robert L. Stephens Kevin V. Hackshaw 《Journal of molecular neuroscience : MN》1996,27(3):315-324
Peripheral nerve injury leads to the activation of spinal cord astrocytes, which contribute to maintaining neuropathic (NP)
pain behavior. Fibroblast growth factor-2 (FGF-2), a neurotrophic and gliogenic factor, is upregulated by spinal cord astrocytes
in response to ligation of spinal nerves L5 and L6 (spinal nerve ligation [SpNL]). To evaluate the contribution of spinal
astroglial FGF-2 to mechanical allodynia following SpNL, neutralizing antibodies to FGF-2 were injected intrathecally. Administration
of 18 μg of anti-FGF-2 antibodies attenuated mechanical allodynia at day 21 after SpNL and reduced FGF-2 and glial acidic
fibrillary protein mRNA expression and immunoreactivity in the L5 spinal cord segment of rats with SpNL. These results suggest
that endogenous astroglial FGF-2 contributes to maintaining NP tactile allodynia associated with reactivity of spinal cord
astrocytes and that inhibition of spinal FGF-2 ameliorates NP pain signs. 相似文献
12.
AbstractGlycine is an amino acid neurotransmitter found in the spinal cord and is closely associated with interneurons that modulate afferent activity. We have previously shown that low segmental glycine concentrations or blockade of normal glycinergic activity lowers the threshold for pain thresholds. In addition, intrathecal glycine infusion increases the pain threshold in animal models of neuropathic pain. However, the role of the glycine receptor in neuropathic pain is not clear and is the basis for the current study. Using a unilateral sciatic nerve constriction injury model of neuropathic pain, the strychnine sensitive glycine receptor population was studied using immunohistochemical techniques. Glycine receptors are reduced in number in the dorsal horn bilaterally in injured animals. Glycine and related compounds are potentially valuable agents for treating chronic pain conditions in humans. A better understanding of glycine-receptor interactions should prove valuable as these compounds are studied in greater depth. [Neural Res 1998; 20: 161–168] 相似文献
13.
Effect of lumbar 5 ventral root transection on pain behaviors: a novel rat model for neuropathic pain without axotomy of primary sensory neurons 总被引:13,自引:0,他引:13
A peripheral nerve injury often causes neuropathic pain but the underlying mechanisms remain obscure. Several established animal models of peripheral neuropathic pain have greatly advanced our understanding of the diverse mechanisms of neuropathic pain. A common feature of these models is primary sensory neuron injury and the commingle of intact axons with degenerating axons in the sciatic nerve. Here we investigated whether neuropathic pain could be induced without sensory neuron injury following exposure of their peripheral axons to the milieu of Wallerian degeneration. We developed a unilateral lumbar 5 ventral root transection (L5 VRT) model in adult rats, in which L5 ventral root fibers entering the sciatic nerve were sectioned in the spinal canal. This model differs from previous ones in that DRG neurons and their afferents are kept uninjured and intact afferents expose to products of degenerating efferent ventral root fibers in the sciatic nerve and the denervated muscles. We found that the L5 VRT produced rapid (24 h after transection), robust and prolonged (56 days) bilateral mechanical allodynia, to a similar extent to that in rats with L5 spinal nerve transection (L5 SNT), cold allodynia and short-term thermal hyperalgesia (14 days). Furthermore, L5 VRT led to significant inflammation as demonstrated by infiltration of ED-1-positive monocytes/macrophages in the DRG, sciatic nerve and muscle fibers. These findings demonstrated that L5 VRT produced behavioral signs of neuropathic pain with high mechanical sensitivity and thermal responsiveness, and suggested that neuropathic pain can be induced without damage to sensory neurons. We propose that neuropathic pain in this model may be mediated by primed intact sensory neurons, which run through the milieu of Wallerian degeneration and inflammation after nerve injury. The L5 VRT model manifests the complex regional pain syndrome in some human patients, and it may provide an additional dimension to dissect out the mechanisms underlying neuropathic pain. 相似文献
14.
Madiai F Goettl VM Hussain SR Clairmont AR Stephens RL Hackshaw KV 《Journal of molecular neuroscience : MN》2005,27(3):315-324
Peripheral nerve injury leads to the activation of spinal cord astrocytes, which contribute to maintaining neuropathic (NP) pain behavior. Fibroblast growth factor-2 (FGF-2), a neurotrophic and gliogenic factor, is upregulated by spinal cord astrocytes in response to ligation of spinal nerves L5 and L6 (spinal nerve ligation [SpNL]). To evaluate the contribution of spinal astroglial FGF-2 to mechanical allodynia following SpNL, neutralizing antibodies to FGF-2 were injected intrathecally. Administration of 18 microg of anti-FGF-2 antibodies attenuated mechanical allodynia at day 21 after SpNL and reduced FGF-2 and glial acidic fibrillary protein mRNA expression and immunoreactivity in the L5 spinal cord segment of rats with SpNL. These results suggest that endogenous astroglial FGF-2 contributes to maintaining NP tactile allodynia associated with reactivity of spinal cord astrocytes and that inhibition of spinal FGF-2 ameliorates NP pain signs. 相似文献
15.
Ye Jiang 《The International journal of neuroscience》2018,128(5):467-471
Phrenic nerve transfer has been a well-established procedure for restoring elbow flexion function in patients with brachial plexus avulsion injury. Concerning about probably detrimental respiratory effects brought by the operation, however, stirred up quite a bit of controversy. We present a case report of the successful application of phrenic nerve as donor to reinnervate the biceps in a septuagenarian with brachial plexus avulsion injury, not accompanied with significant clinical respiratory problem. 相似文献
16.
Pro- and anti-inflammatory cytokine gene expression in rat sciatic nerve chronic constriction injury model of neuropathic pain 总被引:9,自引:0,他引:9
Cytokines may be pathophysiologically involved in hyperalgesia. Uncertainty exists about the types of cytokines and their site of action. To study the role of key pro- and anti-inflammatory cytokines in a chronic constriction model of neuropathic pain, mRNA expression of TNF, IL-1beta, IL-6, and IL-10 was quantified using competitive RT-PCR. Each cytokine mRNA in rat sciatic nerve was examined at days 3, 7, 14, and 45 after chronic constriction injury (CCI). We also undertook behavioral testing of these rats. Thermal warming and touch thresholds were significantly reduced at days 3, 7, and 14 in the CCI group, compared with the sham-operated group. Cytokine gene expression in sciatic nerve was significantly increased at day 7 for IL-1beta and IL-6 and at day 14 for TNF. Expression of IL-10 underwent a gradual and progressive increase, reaching statistical significance at day 45. 相似文献
17.
18.
Wei Li Jian-Xiu Wang Zhong-He Zhou Yao Lu Xiao-Qiu Li Bao-Jun Liu 《Neurological research》2013,35(1):80-85
Objective: A recent study showed that brain-derived neurotrophic factor (BDNF) may play a role in the development of the neuropathic pain resulting from injury to motor efferent fibres, such as that in the ventral root transection (VRT) model. Capsaicin stimulation of afferent fibres was also shown to result in the release of BDNF into the spinal cord. Here, the effects of ablation of capsaicin-sensitive primary afferents (CSPAs) by local application of capsaicin on the sciatic nerve on VRT-induced mechanical hyperalgesia were observed.Methods: The paw withdrawal mechanical threshold (PWMT) was measured before and then 1 and 3 days and 1, 2, 3, 4 and 6 weeks after VRT.Results: The results showed that local application of capsaicin significantly inhibited the decrease in the PWMT induced by VRT, suggesting the inhibitory effect of locally delivered capsaicin. Furthermore, intrathecal administration of exogenous BDNF not only produced mechanical hyperalgesia but also significantly blocked the inhibitory effect of capsaicin.Conclusion: Taken together, the results of this study suggest that CSPA fibres may contribute to mechanical hyperalgesia in the VRT model. 相似文献
19.
20.
Glial cell line-derived neurotrophic factor (GDNF) has been proved to play an important role in the modulation of nociceptive transmission especially during neuropathic pain. It was reported that electroacupuncture (EA) had potent analgesic effect on neuropathic pain and our previous studies indicated that EA could activate endogenous GDNF signaling system (GDNF and its receptor GFRalpha-1) in dorsal root ganglions (DRGs) of neuropathic pain rats. In order to investigate whether GDNF signaling system was involved in EA analgesia on neuropathic pain, which was induced by chronic constriction injury (CCI) of the sciatic nerve in rats, antisense oligodeoxynucleotide (ODN) specifically against GFRalpha-1 was used in the present study to result in down-regulation of GFRalpha-1 expression. The results showed that: (1) cumulative EA had potent analgesic effect on neuropathic pain in rats; (2) the expression of GFRalpha-1 in DRGs was down-regulated by intrathecal delivery of antisense ODN, but not by normal saline (NS) or mismatch ODN; (3) EA analgesia was significantly attenuated by antisense ODN treatment. The present study demonstrated that endogenous GDNF signaling system was involved in EA analgesia on neuropathic pain in rats, which would deepen our realization of the mechanism of EA analgesia. 相似文献