Intraplantar injection of linalool reduces paclitaxel-induced acute pain in mice

Linalool is the principal component of many essential oils known to possess biological activities. We previously reported that intraplantar injection of linalool reduces the nociceptive response as assayed by the capsaicin test. In this study, we sought to determine whether intraplantar injection of linalool could influence the induction of acute pain (allodynia and hyperalgesia) by paclitaxel in mice. Paclitaxel is widely used in cancer chemotherapy for the treatment of solid tumors, but it sometimes induces moderate to severe acute pain. Paclitaxel administered intraperitoneally as a single dose of 5, 10 or 20 mg/kg produced mechanical allodynia and hyperalgesia in mice. Paclitaxel-induced mechanical allodynia and hyperalgesia began 1 day after administration of paclitaxel and resolved within 7 days. Linalool injected into the hindpaw caused a significant reduction in paclitaxel-induced mechanical allodynia and hyperalgesia. Pretreatment with naloxone hydrochloride, an opioid receptor antagonist, or naloxone methiodide, a peripherally acting μ-opioid receptor-preferring antagonist, significantly reversed linalool-induced antiallodynia and antihyperalgesia. Our results provide evidence for the involvement of peripheral opioids in antiallodynia and antihyperalgesia induced by linalool. These results suggest that activation of peripheral opioid receptors may play an important role in reducing paclitaxel-induced mechanical allodynia and hyperalgesia.     

Expectation decreases brain susceptibility to fearful stimuli: ERP evidence from a modified emotion evaluation task

Osteomyelitis is an acute or chronic inflammatory process of bone accompanied with mild to severe pain. Generally, mild to moderate pain induced by osteomyelitis can be relieved, yet severe pain cannot. Therefore, a further investigation into the mechanism of severe pain induced by osteomyelitis is needed. In this study, a traditional rat model of osteomyelitis was induced by intra-tibial injection of Staphylococcus aureus. Then, a series of tests including bone histology, blood analysis, mechanical allodynia, thermal hyperalgesia, and immunohistochemistry were performed. Four days after an intra-tibial bacterial injection, acute inflammation was observed in the bone marrow, which developed into chronic inflammation 12 days after the procedure. The results from the blood analysis confirmed the existence of bone inflammation. Significant mechanical allodynia and thermal hyperalgesia developed shortly after the injection. This osteomyelitis-induced pain behavior was reversed by Celecoxib, a selective COX-2 inhibitor. Furthermore, significant increase of both microglia and astrocytes was observed in the spinal cord. Our results suggest that osteomyelitis-induced rats display pain related behaviors and associated neurochemical changes. This study thus provides a novel practical rat model of bone inflammation induced pain.     

Behavioral, pharmacological and molecular characterization of the saphenous nerve partial ligation: a new model of neuropathic pain

The saphenous partial ligation (SPL) model is a new, easily performed, rodent model of neuropathic pain that consists of a unilateral partial injury to the saphenous nerve. The present study describes behavioral, pharmacological and molecular properties of this model. Starting between 3 and 5 days after surgery, depending on the modality tested, animals developed clear behaviors indicative of neuropathic pain such as cold and mechanical allodynia, and thermal and mechanical hyperalgesia compared with naive and sham animals. These pain behaviors were still present at 1 month. Signs of allodynia also extended to the sciatic nerve territory. No evidence of autotomy or bodyweight loss was observed. Cold and mechanical allodynia but not thermal and mechanical hyperalgesia was reversed by morphine (4 mg/kg i.p.). The cannabinoid receptor agonist WIN 55,212-2 (5 mg/kg i.p.) improved signs of allodynia and hyperalgesia tested except for mechanical hyperalgesia. Gabapentin (50 mg/kg i.p.) was effective against cold and mechanical allodynia but not hyperalgesia. Finally, amitriptyline (10 mg/kg i.p.) failed to reverse allodynia and hyperalgesia and its administration even led to hyperesthesia. Neurobiological studies looking at the expression of mu opioid receptor (MOR), cannabinoid CB(1) and CB(2) receptors showed a significant increase for all three receptors in ipsilateral paw skin, L3-L4 dorsal root ganglia and spinal cord of neuropathic rats compared with naive and sham animals. These changes in MOR, CB(1) and CB(2) receptor expression are compatible with what is observed in other neuropathic pain models and may explain the analgesia produced by morphine and WIN 55,212-2 administrations. In conclusion, we have shown that the SPL is an adequate model that will provide a new tool for clarifying peripheral mechanisms of neuropathic pain in an exclusive sensory nerve.     

Intralesion transplantation of serotonergic precursors enhances locomotor recovery but has no effect on development of chronic central pain following hemisection injury in rats

The effects of intralesion grafts of serotonergic precursors on locomotor recovery and development of chronic pain were assessed after chronic spinal cord hemisection injury (SCI) in rats. Serotonin- and brain-derived neurotrophic factor-secreting (RN46A-B14) and RN46A-vector-only cells were transplanted into the site of T13 lateral hemisection 10 days following injury in immunosuppressed animals, and locomotor and pain related behaviors were assessed weekly for 28 days. There were significant improvements in the degree of spontaneous locomotor recovery, but no significant difference was found in the magnitude of development of mechanical allodynia or thermal hyperalgesia in any transplant group. From these results, we conclude that intraparenchymal engraftment of RN46A-B14 cells is largely ineffective in influencing somatosensory outcomes after SCI, in contrast with the efficacy of dorsal intrathecal placement.     

Perfusion of the mechanically compressed lumbar ganglion with lidocaine reduces mechanical hyperalgesia and allodynia in the rat

The rat L(5) dorsal root ganglion (DRG) was chronically compressed by inserting a hollow perforated rod into the intervertebral foramen. The DRG was constantly perfused through the hollow rod with either lidocaine or normal saline delivered by a subcutaneous osmotic pump. Behavioral evidence for neuropathic pain after DRG compression involved measuring the incidence of hindlimb withdrawals to both punctate indentations of the hind paw with mechanical probes exerting different bending forces (hyperalgesia) and to light stroking of the hind paw with a cotton wisp (tactile allodynia). Behavioral results showed that for saline-treated control rats: the withdrawal thresholds for the ipsilateral and contralateral paws to mechanical stimuli decreased significantly after surgery and the incidence of foot withdrawal to light stroking significantly increased on both ipsilateral and contralateral hind paws. Local perfusion of the compressed DRG with 2% lidocaine for 7 days at a low flow-rate (1 microl/h), or for 1 day at a high flow-rate (8 microl/h) partially reduced the decrease in the withdrawal thresholds on the ipsilateral foot but did not affect the contralateral foot. The incidence of foot withdrawal in response to light stroking with a cotton wisp decreased significantly on the ipsilateral foot and was completely abolished on the contralateral foot in the lidocaine treatment groups. This study demonstrated that compression of the L(5) DRG induced a central pain syndrome that included bilateral mechanical hyperalgesia and tactile allodynia. Results also suggest that a lidocaine block, or a reduction in abnormal activity from the compressed ganglia to the spinal cord, could partially reduce mechanical hyperalgesia and tactile allodynia.     

Co-administration of MK-801 and morphine attenuates neuropathic pain in rat

Partial peripheral nerve injury often leads to chronic pain states, including allodynia and hyperalgesia. The purpose of this study was to investigate the involvement of the N-methyl-D-aspartate and opioid receptors in the behavioural responses following chronic constriction nerve injury (CCI). The animals were injected a combination of MK-801 (0.3 mg/kg, 20 min before, and 6 h after the operation) and morphine (8 mg/kg, 30 min prior to the operation) and were tested for allodynia and hyperalgesia reactions at 0, 3, 7, 14, 21 and 28 days after CCI. Compound action potentials were also recorded from the injured nerve 2 weeks post-operation to indicate nerve injury state electrophysiologically. Our results indicate that the CCI model importantly influences the behavioural responses to both the thermal and mechanical stimulations. Also, the pre-emptive co-administration of MK-801 and morphine has suppressive effects on the cold allodynia but a slight alleviation on the mechano-allodynia and heat hyperalgesia.     

大鼠开胸术后慢性疼痛的预测指标

目的观察疼痛时弥散性伤害抑制性控制(DNIC)的动态变化,对术前DNIC、术后急性疼痛能否作为术后慢性胸痛的预测指标进行初步研究。方法术前检测大鼠DNIC,建立开胸术后慢性疼痛模型,分组为空白组(n=10)、假手术组(n=10)、模型组(n=20),连续监测术后1、3、6、9、12、15、18和21 d的机械痛阈、冷痛阈及DNIC。结果模型组大鼠中,11只发展为慢性疼痛组(CPTP组),9只在经历急性疼痛后痛觉恢复正常(non-CPTP组)。与CPTP组比较,non-CPTP组术前DNIC减弱(P0.05),术后6 d切口附近机械痛阈值及冷痛阈值更低(P0.05)。与术前DNIC相比,模型组术后急性疼痛时期(术后3 d)DNIC减弱(P0.05),CPTP组术后21 d DNIC持续减弱(P0.05),而non-CPTP组DNIC恢复正常。结论术前DNIC及术后6 d急性疼痛程度是开胸术后慢性疼痛的两项危险因素;疼痛急性期,个体DNIC减弱,痛觉恢复正常时,个体DNIC水平也渐趋恢复正常。     

Lysophosphatidylcholine induces neuropathic pain through an action of autotaxin to generate lysophosphatidic acid

Lysophosphatidic acid receptor (LPA(1)) signaling initiates neuropathic pain and several pathological events in a partial sciatic nerve injury model. Recently, we reported that lysophosphatidic acid (LPA) induces neuropathic pain as well as demyelination and pain-related protein expression changes via LPA(1) receptor signaling. Lysophosphatidylcholine (LPC), also known as lysolecithin, which is hydrolyzed by autotaxin/ATX into LPA, induces similar plastic changes. Here, we attempted to clarify whether ATX and LPA(1) receptor signaling is involved in the LPC-induced neuropathic pain. In wild-type mice, a single intrathecal (i.t.) injection of LPC induced mechanical allodynia and thermal hyperalgesia 2 days after injection; this persisted for 7 days at least. On the other hand, LPC-induced mechanical allodynia and thermal hyperalgesia were completely abolished in mice lacking an LPA(1) receptor gene. Furthermore, the LPC-induced response was also significantly, but partially reduced in heterozygous mutant mice for the ATX gene. These findings suggest that intrathecally-injected LPC is converted to LPA by ATX, and this LPA activates the LPA(1) receptor to initiate neuropathic pain.     

A rat model of bone inflammation-induced pain by intra-tibial complete Freund's adjuvant injection

In prior studies, models of inflammatory pain were produced through injecting complete Freund's adjuvant (CFA) or capsaicin directly into either the deep somatic tissue or the animal's hind paw. In contrast, bone cancer-induced pain (BCIP) was simulated through injecting tumor cells into the cavity of the femur or the tibia. It has been reported that, due to differences in afferent innervation, the same stimulus to various tissue types might result in differing patterns of pain response. Hence, the aim of this study is to establish a rat model of bone inflammation-induced pain (BIIP) by injecting CFA into the tibial cavity, the same site involved in the BCIP model. The differences in body weight, bone histology, mechanical allodynia, thermal hyperalgesia, and the pain relieving effects of Celebrex on this model of BIIP were evaluated. The results showed that there was evidence of significant inflammation seen in the bone marrow two days after intra-tibial CFA injection, including nuclear condensation and fragmentation, massive neutrophilic granulocytes, and prominent fibrinous exudates. Fourteen days after injection, marked fibrosis of the bone was detected by histological staining. After unilateral CFA injection, behavioral studies showed mechanical allodynia to von Frey hair stimulation, but no thermal hyperalgesia was observed. Celebrex showed significant anti-allodynic effects on the BIIP model. The results demonstrated that CFA is an effective agent for inducing bone inflammation and subsequent pain-related behavior in rat models, and, thus, provides a practical and valuable contrast for BCIP research.     

Interleukin-17 levels in rat models of nerve damage and neuropathic pain

In the present study, we assessed IL-17 levels at 3 and 8 days following various forms of injuries to the sciatic nerve and related the cytokine levels to the pain behaviors associated with the injuries. The four experimental models employed were chronic constriction injury (CCI), partial sciatic ligation (PSL), complete sciatic transection (CST) and perineural inflammation (Neuritis). Behavior withdrawal thresholds for mechanical stimulus and withdrawal latency for thermal stimulation were used to measure mechanical allodynia and thermal hyperalgesia. IL-17 levels of the affected, contralateral and naïve rats’ sciatic nerve were assessed employing enzyme-linked immunosorbent assay (ELISA). Rats exposed to CCI and Neuritis displayed significant mechanical allodynia and thermal hyperalgesia 3, 5 and 8 days following the procedure, rats exposed to PSL displayed significant mechanical allodynia 5 and 8 days following the procedure and rats exposed to CST developed significant hypoesthesia. Three days following the procedure, IL-17 levels increased significantly compared to naïve rats only in the PSL model. Eight days following the procedure, IL-17 levels in nerves exposed to CCI, CST, PSL and Neuritis were significantly elevated compare to intact nerve levels. It is likely that IL-17 has a limited role in the acute phase of nerve injury and the associated acute pain, but may have a role in later phases of the processes of the development of neuropathic pain.     

Transient early expression of TNF-alpha in sciatic nerve and dorsal root ganglia in a mouse model of painful peripheral neuropathy

The proinflammatory cytokine tumor necrosis factor-alpha (TNF) is an important mediator in neuropathic pain. We investigated the temporal pattern of TNF mRNA expression in the sciatic nerve, in dorsal root ganglia (DRG) and spinal cord in the mouse chronic constriction injury model of neuropathy with quantitative real-time polymerase chain reaction. Neuropathic pain-like behaviour was monitored by evaluating thermal hyperalgesia and mechanical allodynia. Pain-related behaviour and TNF expression were evaluated 6 h, 1, 3, 7 and 14 days after injury. Naive animals and sham-operated mice were used as controls. We found an early upregulation of sciatic nerve TNF mRNA levels in chronic constriction injury (CCI) and sham-operated animals 6 h after surgery: 1 day later TNF overexpression was present in CCI mice only and disappeared 3 days after injury. The mRNA cytokine levels were elevated in DRG 1 and 3 days after surgery in CCI animals only, while the cytokine was not modulated in the spinal cord. A significant hyperalgesia was present in CCI and sham-operated mice at 6 h and 1 day, while at later time point only CCI mice presented lower thresholds. Mechanical allodynia was already present only in CCI animals 6 h from surgery and remained constant up to the 14 th day. The results indicate that a transient early TNF upregulation takes place in peripheral nervous system after CCI that can activate a cascade of proinflammatory/pronociceptive mediators.     

Modulation of P2X receptors in dorsal root ganglion neurons of streptozotocin-induced diabetic neuropathy

Painful diabetic neuropathy causes hyperalgesia and does not respond to commonly used analgesics such as non-steroidal anti-inflammatory drugs or opioids at doses below those producing disruptive side effects. In the present study, we examined the effect of P2X receptor antagonists, which are known to modulate the pain pathway, on mechanical hyperalgesia in streptozotocin (STZ)-induced diabetic mice. The paw withdrawal frequency measured by von Frey filaments, began to significantly increase 5 days after STZ injection and was maintained for more than 14 days. Intrathecal administration of P2X receptor antagonists (PPADS and TNP-ATP) inhibited the mechanical allodynia in diabetic mice. The levels of P2X₂ and P2X₃ receptors mRNA were significantly increased in diabetic mice at 14 days after the intravenous injection of STZ. These results suggest that the upregulation of P2X₂, P2X₃ and/or P2X_2/3 receptor in DRG neurons is associated with mechanical allodynia in STZ-induced diabetic mice.     

外周炎性痛刺激诱导杏仁核内星形胶质细胞激活及细胞因子的表达

为了观察完全弗氏佐剂(CFA)外周刺激对杏仁核内星形胶质细胞标记物(GFAP)以及细胞因子(IL-β,TNF-α)表达的影响,本研究结合行为学检测、RT-PCR和Westernblot方法,观察了大鼠后爪注射CFA后的痛行为变化,并检测了在不同时间点杏仁核内GFAP、IL-β和TNF-α在基因水平和蛋白水平的表达变化。结果显示:注射CFA后,注射侧后爪出现热痛敏和机械性触诱发痛;大鼠的热痛敏在14d时基本恢复正常,但机械性痛敏持续至21d时仍未恢复正常;GFAP在亚急性期和慢性期有显著增加;而IL-β和TNF-α在急性期、亚急性期及慢性期均有增加。上述结果表明:星形胶质细胞可能与疼痛的维持相关,而细胞因子表达的增加可能在痛觉过敏的产生和维持中均起重要作用。     

MiR-19a targets suppressor of cytokine signaling 1 to modulate the progression of neuropathic pain

Purpose: we aimed to investigate whether miR-19a is associated with neuropathic pain and elucidate the underlying regulatory mechanism. Methods: We established a neuropathic pain model of bilateral chronic constriction injury (bCCI). Then bCCI rats were injected with mo-miR-19a, siR-SOCS1 or blank expression vector through a microinjection syringe via an intrathecal catheter on 3 day before surgery and after surgery. Behavioral tests, such as mechanical allodynia, thermal hyperalgesia and acetone induced cold allodynia, were performed to evaluate the pain threshold. Besides, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the expression of miR-19a and western blotting was carried out to measure the expression of SOCS1. Results: miR-19a expression levels were markedly increased in neuropathic pain models. Moreover, miR-19a significantly attenuated mechanical allodynia and thermal hyperalgesia, and similar results were obtained after knockdown of SOCS1 expression. However, miR-19a markedly increased the times that the rats appeared a sign of cold allodynia, and knockdown of SOCS1 expression had similar effects. Besides, the results of bioinformatics analysis and western blotting analysis were all confirmed that SOCS1 was a direct target of miR-19a in neuropathic pain models. Conclusions: Our finding indicate that SOCS1 is a direct target of miR-19a in neuropathic pain rats and miR-19a may play a critical role in regulating of neuropathic pain via targeting SOCS1.     

Local application of capsaicin alleviates mechanical hyperalgesia after spinal nerve transection

Whether modulation of C afferent fiber activities could relieve peripheral neuropathic pain was tested. After establishment of neuropathic pain induced by L5 and 6 spinal nerve transection (SNT), the sciatic nerve was treated with 2% capsaicin at the level of the midthigh. Mechanical hyperalgesia (von Frey filaments) was significantly alleviated from 7 days to 4 weeks after capsaicin treatment, but cold allodynia (acetone) was unchanged. Immunohistochemical studies showed a significant increase in the number of calcitonin gene-related peptide (CGRP)-positive neurons, but not TRPV1-positive neurons in intact L4 dorsal root ganglia after SNT. Capsaicin treatment decreased TRPV1- and CGRP-positive neurons in L4 DRG of the treated side, but not the opposite side. These results suggest that local application of capsaicin onto the sciatic nerve can alleviate mechanical hyperalgesia, but not cold allodynia, in a peripheral neuropathic pain model and the pain alleviation may result from a decrease of TRPV1- and CGRP-positive sensory neurons of which fibers pass through the sciatic nerve.     

Antiallodynic effects of acupuncture in neuropathic rats

Peripheral nerve injury often results in abnormal neuropathic pain such as allodynia or hyperalgesia. Acupuncture, a traditional Oriental medicine, has been used to relieve pain and related symptoms. However, the efficiency of acupuncture in relieving neuropathic pain is not clear. The aim of this study was to investigate the anti-allodynic effects of acupuncture through behavioral and electrophysiological examinations. Male Sprague-Dawley rats were subjected to neuropathic surgery consisting of a tight ligation and transection of the left tibial and sural nerves, under pentobarbital anesthesia. The acupuncture experiment consisted of four different groups, one treated at each of three different acupoints (Zusanli (ST36), Yinlingquan (SP9), and a sham-acupoint) and a control group. Behavioral tests for mechanical allodynia and cold allodynia were performed for up to two weeks postoperatively. Extracellular electrophysiological recordings were made from the dorsal roots using platinum wire electrodes. Mechanical and cold allodynia were significantly reduced after acupuncture treatment at the Zusanli and Yinlingquan acupoints, respectively. Electrophysiological neural responses to von Frey and acetone tests were also reduced after acupuncture at the same two acupoints. These results suggest that acupuncture may be beneficial in relieving neuropathic pain.     

Enhanced excitability of sensory neurons in rats with cutaneous hyperalgesia produced by chronic compression of the dorsal root ganglion

Pain and hyperalgesia can occur when the dorsal root ganglion (DRG) and its roots are deformed mechanically in association with injuries or diseases of the spine. To evaluate the electrophysiological changes that contribute to this sensory pathology, intracellular recordings were obtained in vitro from DRGs that had received a chronic mechanical compression [chronic compression of DRG (CCD)]. The compression was produced by inserting L-shaped rods ipsilaterally into the intervertebral foramina, one at L(4) and the other at L(5) in rats 1-14 days before the recording. Control rats received a sham operation. Postoperatively, the threshold force applied by punctate stimulation of the plantar surface of the hind paw decreased significantly on the foot ipsilateral to the CCD (mechanical hyperalgesia) but changed little on the contralateral foot or on either foot for control rats. DRG somata were viewed through a microscope during recording and classified as small, medium, and large according to their diameters. CCD cells in each size category were more excitable than those of comparable size from control rats as judged by the significantly lowered threshold currents and action potential voltage thresholds. Spontaneous activity was recorded in 11% of all the CCD cells tested. The spontaneous activity and/or changes in both the threshold currents and action potential thresholds were observed as early as one day after injury. The association of cutaneous hyperalgesia with changes in the electrophysiological properties of DRG cells suggests a possible role for intrinsic alterations in the membrane properties of compressed DRG cells in the production and persistence of chronic pain after certain spinal injuries or pathologies of the spine.     

Acute and chronic ethanol does not affect incisional pain in neonatal rats

We have previously found that in post-natal day 7 rats withdrawal from acute and chronic ethanol (EtOH) exposure lowers mechanical thresholds during withdrawal and exacerbates spontaneous pain responses to an inflammatory injury 4 days post-withdrawal. These findings suggested alterations in somatosensory pathways following EtOH exposure during the third trimester developmental equivalent. In this study we wanted to determine whether EtOH exposure during the third trimester equivalent exacerbates mechanical allodynia and thermal hyperalgesia produced by an incisional model of post-operative pain at post-natal day 21. The extent and duration of mechanical allodynia and thermal hyperalgesia following incision was measured and found to be unaffected by prior EtOH exposure.     

Morphine tolerance attenuates the resolution of postoperative pain and enhances spinal microglial p38 and extracellular receptor kinase phosphorylation

Persistent postoperative pain is a very common phenomenon which severely affects the lives of patients who develop it following common surgical procedures. Opioid analgesics are of limited efficacy in the treatment of persistent pain states because of side effects including antinociceptive tolerance. We have previously shown that surgical incision injury and morphine tolerance share similar mechanisms, including a CNS role of spinal cord glia. We therefore hypothesized that prior chronic morphine exposure would inhibit the resolution of postoperative allodynia through increased glial ionized calcium-binding adaptor protein 1 (Iba1) and glial fibrillary acidic protein (GFAP) protein expression and mitogen activated protein kinase (MAPK) activation. To test this hypothesis, rats were implanted with s.c. osmotic minipumps on day zero, releasing saline or morphine for 7 days preceding or 7 days preceding and following paw incision surgery, which was completed on day seven. Thermal hyperalgesia and mechanical allodynia were assessed postoperatively every 3 days. Chronic morphine attenuated the resolution of postoperative thermal hyperalgesia and mechanical allodynia through day 20. However, no changes in Iba1 or GFAP expression were observed in the spinal cord dorsal horn between groups. Assessment of MAPK protein phosphorylation revealed that chronic morphine administration enhanced both p38 and extracellular receptor kinase (pERK) phosphorylation compared to saline on day 20. p-p38 and pERK immunofluorescence were only observed to colocalize with a marker of microglial cells and not with markers of astrocytes or neurons. Together, these data demonstrate that chronic morphine administration attenuates the resolution of postoperative allodynia in association with microglial p38 and extracellular receptor kinase (ERK) phosphorylation, independent of changes in Iba1 and GFAP expression.     

A novel human foamy virus mediated gene transfer of GAD67 reduces neuropathic pain following spinal cord injury

Neuropathic pain is a long-lasting clinical problem that is often refractory to medical management. Gene transfer of specific genes for therapeutic benefit offers a novel approach to the treatment of neuropathic pain. In this study, we tested whether the transfer of the glutamic acid decarboxylase (GAD) gene to dorsal root ganglion (DRG) cells would attenuate below-injury level central neuropathic pain after spinal cord injury (SCI) by using a novel human foamy virus (HFV) vector to achieve release of gamma-aminobutyric acid (GABA). Subcutaneous inoculation of a replication-defective HFV vector, which expresses GAD (vector rdvGAD67) for 7days after T13 spinal cord hemisection, reversed mechanical allodynia and thermal hyperalgesia evoked by SCI. The antiallodynic effect lasted 6 weeks and was reestablished by reinoculation. We also found that subcutaneous inoculation of rdvGAD67 resulted in enhanced production of GAD and tonical GABA release from transduced DRG neurons. These results suggest that HFV-mediated gene transfer to DRG could be employed to treat below-injury level central neuropathic pain after incomplete SCI.