Unilateral Sciatic Nerve Injury Research Articles

Comparison of the Effects of Electroacupuncture and Melatonin on Nerve Regeneration in Experimentally Nerve-Damaged Rats.

Development of methods to accelerate nerve regeneration in peripheral nerve damage is important. Electroacupuncture is a new therapeutic method that combines traditional acupuncture with modern electrotherapy. Melatonin has been shown to reduce nerve damage. Objectives: In this study, we aimed to determine and compare the therapeutic effects of electroacupuncture and melatonin on rat sciatic nerve injury. A total of 56 adult male Wistar Albino rats were divided into four study groups with 14 animals in each group: intact control (group I), subcutaneous saline (group II), subcutaneous melatonin (group III), and electroacupuncture (group IV). Surgical procedure including unilateral (right) sciatic nerve injury was applied to groups II, III, and IV. Saline and melatonin started immediately after surgery for six weeks, while electroacupuncture was given two weeks after surgery for 3 weeks. Functional and histological assessments were used as outcome measurements. Sciatic nerve damage caused a significant decrease in nerve conduction velocity. Both electroacupuncture treatment and melatonin treatment significantly increased the nerve conduction velocity. Both sciatic functional recovery and histological regeneration were faster in these treatment groups compared to the saline. However, no significant difference was observed between the two treatment groups. Electroacupuncture and melatonin are promising alternative treatment strategies for peripheral nerve damage and can be examined in detail in future studies.

Extracorporeal shockwave therapy enhances peripheral nerve remyelination and gait function in a crush model.

Conservative treatment, such as electrical stimulation and steroid injection, have been employed in an attempt to improve symptoms after peripheral nerve injury, without significant success. Although non-invasive and safe extracorporeal shockwave therapy (ESWT) can be a practical alternative, the therapeutic effects of ESWT on peripheral nerve remyelination has not been established. To investigate the effects of ESWT on peripheral nerve remyelination and gait function for 5 weeks in a sciatic nerve crush model. In total, we divided 97 rats into 5 groups: group 1 - a healthy negative control group; group 2 - 3 weeks after sciatic nerve crush and 3 sessions of ESWT; group 3 - 5 weeks after crush injury with 3 sessions of ESWT; group 4 - 3 weeks after crush injury with no ESWT; and group 5 - 5 weeks after crush injury with no ESWT. The focused ESWT was applied to the unilateral sciatic nerve injury site. One session consisted of 1,500 stimuli, and the session were performed at intervals of 1 week. The degree of myelination and expression of myelin basic protein at the distal part of the injured sciatic nerve tended to increase in the ESWT groups compared with the no-ESWT groups 3 and 5 weeks after crush injury. Regarding the functional gait recovery, the print width and area of the injured leg in the ESWT groups was significantly larger than that in the no-ESWT groups 3 and 5 weeks after crush injury. The ESWT may enhance peripheral nerve remyelination and gait function in a nerve crush model. Long-term follow-up after ESWT and investigation of molecular mechanisms will be needed to confirm these therapeutic effects.

Effects of brazilein on PSD-95 protein expression and neurological recovery in mice after sciatic nerve injury

PurposeTo evaluate the local nerve myelin recovery and the expression of PSD-95 protein and mRNA in the L4–L6 segment of the spinal cord after applying Brazilein to sciatic nerve injury BALB/c mice model and investigate the regulatory effects of Brazilein on myelin recovery after peripheral nerve injury. MethodsA total of 160 BALB/c mice were selected to establish the unilateral sciatic nerve injury model and randomly divided into four groups: saline blank control, Brazilein high-dose, medium-dose, and low-dose. Mice were assessed at different time points (1 w, 2 w, 4 w, 8 w) after sciatic nerve injury for the sciatic functional index (SFI) and sciatic nerve function recovery of the injured side by myelin Luxol Fast Blue (LFB) staining of the sciatic nerve. In addition, immunohistochemistry, real time-PCR, and Western blot were used to detect the PSD-95 expression in the spinal cord L4–L6 segments of the injured sciatic nerve at each time point. ResultsThe results of SFI and sciatic nerve function recovery, as well as, myelin LFB staining of the injured side indicated that all indexes of the Brazilein middle- and high-dose groups were significantly better than the low-dose and blank control groups at each time point. The PSD-95 expression in the L4–L6 segment of the spinal cord was statistically lower in the high- and medium-dose groups than in the low-dose and blank control groups at 1 w, 2 w, and 4 w, while the differences between the groups were not significant at 8 w. ConclusionBrazilein inhibits PSD-95 activation in the corresponding segment of sciatic nerve spinal cord in BALB/c mice after sciatic nerve injury, thereby inhibiting the excessive expression of free radicals and promoting myelin regeneration.

Interleukin-6 contributes to initiation of neuronal regeneration program in the remote dorsal root ganglia neurons after sciatic nerve injury.

To assess the potential role of IL-6 in sciatic nerve injury-induced activation of a pro-regenerative state in remote dorsal root ganglia (DRG) neurons, we compared protein levels of SCG-10 and activated STAT3, as well as axon regeneration in IL-6 knockout (IL-6ko) mice and their wild-type (WT) counterparts. Unilateral sciatic nerve compression and transection upregulated SCG-10 protein levels and activated STAT3 in DRG neurons not only in lumbar but also in cervical segments of WT mice. A pro-regenerative state induced by prior sciatic nerve lesion in cervical DRG neurons of WT mice was also shown by testing for axon regeneration in crushed ulnar nerve. DRG neurons from IL-6ko mice also displayed bilaterally increased levels of SCG-10 and STAT3 in both lumbar and cervical segments after sciatic nerve lesions. However, levels of SCG-10 protein in lumbar and cervical DRG of IL-6ko mice were significantly lower than those of their WT counterparts. Sciatic nerve injury induced a lower level of SCG-10 in cervical DRG of IL-6ko than WT mice, and this correlates with significantly shorter regeneration of axons distal to the crushed ulnar nerve. These results suggest that IL-6 contributes, at the very least, to initiation of the neuronal regeneration program in remote DRG neurons after unilateral sciatic nerve injury.

A Conditioning Sciatic Nerve Lesion Triggers a Pro-regenerative State in Primary Sensory Neurons Also of Dorsal Root Ganglia Non-associated With the Damaged Nerve.

The primary sensory neurons of dorsal root ganglia (DRG) are a very useful model to study the neuronal regenerative program that is a prerequisite for successful axon regeneration after peripheral nerve injury. Seven days after a unilateral sciatic nerve injury by compression or transection, we detected a bilateral increase in growth-associated protein-43 (GAP-43) and superior cervical ganglion-10 (SCG-10) mRNA and protein levels not only in DRG neurons of lumbar spinal cord segments (L4-L5) associated with injured nerve, but also in remote cervical segments (C6-C8). The increase in regeneration-associated proteins in the cervical DRG neurons was associated with the greater length of regenerated axons 1 day after ulnar nerve crush following prior sciatic nerve injury as compared to controls with only ulnar nerve crush. The increased axonal regeneration capacity of cervical DRG neurons after a prior conditioning sciatic nerve lesion was confirmed by neurite outgrowth assay of in vitro cultivated DRG neurons. Intrathecal injection of IL-6 or a JAK2 inhibitor (AG490) revealed a role for the IL-6 signaling pathway in activating the pro-regenerative state in remote DRG neurons. Our results suggest that the pro-regenerative state induced in the DRG neurons non-associated with the injured nerve reflects a systemic reaction of these neurons to unilateral sciatic nerve injury.

Expression of Regeneration-Associated Proteins in Primary Sensory Neurons and Regenerating Axons After Nerve Injury-An Overview.

Peripheral nerve injury results in profound alterations of the affected neurons resulting from the interplay between intrinsic and extrinsic molecular events. Restarting the neuronal regenerative program is an important prerequisite for functional recovery of the injured peripheral nerve. The primary sensory neurons with their cell bodies in the dorsal root ganglia provide a useful in vivo and in vitro model for studying the mechanisms that regulate intrinsic neuronal regeneration capacity following axotomy. These studies frequently need to indicate the regenerative status of the corresponding neurons. We summarize the critical issues regarding immunohistochemical detection of several regeneration-associated proteins as markers for the initiation of the regeneration program in rat primary sensory neurons and indicators of axon regeneration in the peripheral nerves. This overview also includes our own results of GAP43 and SCG10 expression in different DRG neurons following double immunostaining with molecular markers of neuronal subpopulations (NF200, CGRP, and IB4) as well as transcription factors (ATF3 and activated STAT3) following unilateral sciatic nerve injury. Anat Rec, 301:1618-1627, 2018. © 2018 Wiley Periodicals, Inc.

Bilateral activation of STAT3 by phosphorylation at the tyrosine-705 (Y705) and serine-727 (S727) positions and its nuclear translocation in primary sensory neurons following unilateral sciatic nerve injury.

Unilateral sciatic nerve compression (SNC) or complete sciatic nerve transection (CSNT), both varying degrees of nerve injury, induced activation of STAT3 bilaterally in the dorsal root ganglia (DRG) neurons of lumbar (L4-L5) as well as cervical (C6-C8) spinal cord segments. STAT3 activation was by phosphorylation at the tyrosine-705 (Y705) and serine-727 (S727) positions and was followed by their nuclear translocation. This is the first evidence of STAT3(S727) activation together with the well-known activation of STAT3(Y705) in primary sensory neurons upon peripheral nerve injury. Bilateral activation of STAT3 in DRG neurons of spinal segments anatomically both associated as well as non-associated with the injured nerve indicates diffusion of STAT3 activation inducers along the spinal cord. Increased levels of IL-6 protein in the CSF following nerve injury as well as activation and nuclear translocation of STAT3 in DRG after intrathecal injection of IL-6 shows that this cytokine, released into the subarachnoid space can penetrate the DRG to activate STAT3. Previous results on increased bilateral IL-6 synthesis and the present manifestation of STAT3 activation in remote DRG following unilateral sciatic nerve injury may reflect a systemic reaction of the DRG neurons to nerve injury.

Functional recovery following peripheral nerve injury in the transgenic Thy1‐GFP rat

Transgenic mice have been previously used to assess nerve regeneration following peripheral nerve injury. However, mouse models are limited by their small caliber nerves, short nerve lengths, and their inability to fully participate during behavioral assessments. The transgenic Thy1 GFP rat is a novel transgenic rat model designed to assess regeneration following peripheral nerve injury. However, return of functional and behavioral recovery following nerve injury has not yet been evaluated in these rats. In this study, we ask whether differences in anatomy, recovery of locomotion, myological, and histomorphological measures exist between transgenic Thy1 GFP rats when compared to wild type (WT) Sprague Dawley rats following unilateral sciatic nerve injury. We found that both motor and sensory neuronal architecture, overground and skilled locomotion, muscle force, motor unit number estimation (MUNE) and wet muscle weights, and histomorphometric assessments are similar between both genetic phenotypes. Overall, these data support the use of the transgenic Thy1-GFP rat in experiments assessing functional and behavioral recovery following nerve injury and repair.

The State of the Contralateral Gastrocnemius Muscle Motor Center in Rats with Unilateral Sciatic Nerve Injury

The effects of unilateral crushing of the sciatic nerve on the spinal motor center of the contralateral gastrocnemius muscle were studied in rats. At 1, 5, and 10 days after nerve injury, the state of the center of the contralateral gastrocnemius muscle was assessed by paired-pulse monosynaptic testing and evaluation of the post-tetanic potentiation of its reflex response. The results identified changes in the excitability of the contralateral motor center in these conditions. Activation of reflex systems associated with injuries appears to promote a regenerative reorganization of motor control after trauma.

Therapeutic Effect of Myogenic Cells Modified to Express Neurotrophic Factors in a Rat Model of Sciatic Nerve Injury

Sciatic nerve injury may cause neurological deficits, particularly muscle weakness. Previous studies have shown that administration of neurotrophic factors (NTFs), naturally occurring proteins that support the development and survival of neurons, partially protected the damaged motor neuron in the injured sciatic nerve. In the current study, we have examined whether the administration of various combinations of transfected muscle progenitor cells (MPCs) populations, each expressing a single NTF (BDNF, GDNF, IGF-1 or VEGF) or conditioned media of such culture are capable of rescuing motor neurons in culture or in vivo. We have found that the mixture of conditioned media collected from cultured myogenic cells (MPCs- MIX(+)) alleviated the toxic effect of exposure of the motor neuron cell line NSC34 to hypoxic environment. Furthermore, NTFs secreting cells transplantation, protected motor neurons in a unilateral rat sciatic nerve injury model: One day after the crush, rats underwent transplantation at the lesion site with rat myogenic cells expressing one of the four NTFs; a mixture of cells expressing all four NTFs (MPCs- MIX(+)), MPCs-GFP or PBS. We found that in rats injected with MPCs- MIX(+) the motor function was markedly preserved, compared to groups injected with cells secreting a single NTF, GFP or PBS. Transplantation of the MPCs- MIX(+) significantly inhibited the degeneration of the neuromuscular junctions and enhanced the survival of the myelinated motor axons. The injection of MPCs- MIX(+) preserved the compound muscle action potential (CMAP) as was demonstrated by motor nerve conduction studies. Our findings suggest that MPCs induced to secrete several NTFs can synergistically alleviate symptoms of sciatic nerve injury and perhaps other motor neuron disorders..

Somatosensory evoked potential from S1 nerve root stimulation

The objective of this study was to detect cerebral potentials elicited by proximal stimulation of the first sacral (S1) nerve root at the S1 dorsal foramen and to investigate latency and amplitude of the first cerebral potential. Tibial nerve SEP and S1 nerve root SEP were obtained from 20 healthy subjects and 5 patients with unilateral sciatic nerve or tibial nerve injury. Stimulation of the S1 nerve root was performed by a needle electrode via the S1 dorsal foramen. Cerebral potentials were recorded twice to document reproducibility. Latencies and amplitudes of the first cerebral potentials were recorded. Reproducible cerebral evoked potentials were recorded and P20s were identified in 36 of 40 limbs in the healthy subjects. The mean latency of P20 was 19.8 ± 1.6 ms. The mean amplitude of P20-N30 was 1.2 ± 0.9 μV. In the five patients, P40 of tibial nerve SEP was absent, while well-defined cerebral potentials of S1 nerve root SEP were recorded and P20 was identified from the involved side. This method may be useful in detecting S1 nerve root lesion and other disorders affecting the proximal portions of somatosensory pathway. Combined with tibial nerve SEP, it may provide useful information for diagnosis of lesions affecting the peripheral nerve versus the central portion of somatosensory pathway.

Spatio-temporal changes of SDF1 and its CXCR4 receptor in the dorsal root ganglia following unilateral sciatic nerve injury as a model of neuropathic pain

There is a growing evidence that chemokines and their receptors play a role in inducing and maintaining neuropathic pain. In the present study, unilateral chronic constriction injury (CCI) of rat sciatic nerve under aseptic conditions was used to investigate changes for stromal derived factor-1 (SDF1) and its CXCR4 receptor in lumbal (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) from both sides of naïve, CCI-operated and sham-operated rats. All CCI-operated rats displayed mechanical allodynia and thermal hyperalgesia in hind paws ipsilateral to CCI, but forepaws exhibited only temporal changes of sensitivity not correlated with alterations in SDF1 and CXCR4 proteins. Naïve DRG displayed immunofluorescence for SDF1 (SDF1-IF) in the satellite glial cells (SGC) and CXCR4-IF in the neuronal bodies with highest intensity in small- and medium-sized neurons. Immunofluorescence staining and Western blot analysis confirmed that unilateral CCI induced bilateral alterations of SDF1 and CXCR4 proteins in both L4-L5 and C7-C8 DRG. Only lumbal DRG were invaded by ED-1+ macrophages exhibiting SDF1-IF while elevation of CXCR4-IF was found in DRG neurons and SGC but not in ED-1+ macrophages. No attenuation of mechanical allodynia, but reversed thermal hyperalgesia, in ipsi- and contralateral hind paws was found in CCI-operated rats after i.p. administration of CXCR4 antagonist (AMD3100). These results indicate that SDF1/CXCR4 changes are not limited to DRG associated with injured nerve but that they also spread to DRG non-associated with such nerve. Functional involvement of these alterations in DRG non-associated with injured nerve in neuropathic pain remains to be elucidated.

Behavioral and Anatomical Characterization of the Bilateral Sciatic Nerve Chronic Constriction (bCCI) Injury: Correlation of Anatomic Changes and Responses to Cold Stimuli

BackgroundUnilateral constrictive sciatic nerve injury (uCCI) is a common neuropathic pain model. However, the bilateral constrictive injury (bCCI) model is less well studied, and shows unique characteristics. In the present study, we sought to correlate effects of bCCI on nocifensive responses to cold and mechanical stimuli with selected dorsal horn anatomic markers. bCCI or sham ligation of both rat sciatic nerves were followed up to 90 days of behavioural testing. Additional rats sacrificed at 15, 30 and 90 days were used for anatomic analyses. Behavioural tests included hindpaw withdrawal responses to topical acetone, cold plate testing, an operant thermal preference task and hindpaw withdrawal thresholds to mechanical probing.ResultsAll nocifensive responses to cold increased and remained enhanced for >45 days. Mechanical withdrawal thresholds decreased for 25 days only. Densitometric analyses of immunoperoxidase staining in the superficial dorsal horn at L4-5 revealed decreased cholecystokinin (CCK) staining at all times after bCCI, decreased mu opiate receptor (MOR) staining, maximal at 15 days, increased neuropeptide Y (NPY) staining only at days 15 and 30, and increased neurokinin-1 receptor (NK-1R) staining at all time points, maximal at 15 days. Correlation analyses at 45 days post-bCCI, were significant for individual rat nocifensive responses in each cold test and CCK and NK-1R, but not for MOR or NPY.ConclusionsThese results confirm the usefulness of cold testing in bCCI rats, a new approach using CCI to model neuropathic pain, and suggest a potential value of studying the roles of dorsal horn CCK and substance P in chronic neuropathic pain. Compared to human subjects with neuropathic pain, responses to cold stimuli in rats with bCCI may be a useful model of neuropathic pain.

Effects of Unilateral Sciatic Nerve Injury on Unaffected Hindlimb Muscles of Rats

The purpose of this study was to examine the effects of unilateral sciatic nerve injury on unaffected hindlimb muscles of rats. Adult male Sprague-Dawley rats were assigned to one of three groups: control (C) group (n=10) that had no procedures, sham (S) group (n=10) that underwent sham left sciatic nerve transection, and sciatic nerve transection (SNT) group (n=9) that underwent left sciatic nerve transection. At 15 days rats were anesthetized, and the soleus, plantaris and gastrocnemius muscles were dissected. Muscle weight of the unaffected plantaris muscle in the SNT group was significantly lower than in the other two groups. Type II fiber cross-sectional areas of the unaffected plantaris and gastrocnemius muscles in the SNT group were significantly smaller than in the other two groups. The decrease of muscle weights and Type I, II fiber cross-sectional areas of the unaffected three muscles in the SNT group were significantly less than that of the affected three muscles. Hindlimb muscle atrophy occurs in the unaffected side after unilateral sciatic nerve injury, with changes in the plantaris and gastrocnemius muscle being more apparent than changes in the soleus muscle. These results have implications for nursing care, in the need to assess degree of muscle atrophy in unaffected muscles as well as affected muscles.

Upregulation of Ryk expression in rat dorsal root ganglia after peripheral nerve injury

To study changes of Ryk expression in dorsal root ganglia (DRG) after peripheral nerve injury, we set up an animal model of unilateral sciatic nerve lesioned rats. Changes of Ryk protein expression in DRG neurons after unilateral sciatic nerve injury were investigated by immunostaining. Changes of Ryk mRNA were also tested by semi-quantitative PCR concurrently. We found, both at the level of protein and mRNA, that Ryk could be induced in cells of ipsilateral DRG after unilateral sciatic nerve lesion. Further investigation by co-immunostaining confirmed that the Ryk-immunoreactive (Ryk-IR) cells were NeuN-immunoreactive (NeuN-IR) neurons of DRG. We also showed the pattern of Ryk induction in DRG neurons after sciatic nerve injury: the number of Ryk IR neurons peaked at 2 weeks post-lesion and decreased gradually by 3 weeks post-lesion. The proportions of different sized Ryk IR neurons were also observed and counted at various stages after nerve lesion. Analysis of Ryk mRNA by RT-PCR showed the same induction pattern as by immunostaining. Ryk mRNA was not expressed in normal or contralateral DRG, but was expressed 1, 2 and 3 weeks post-lesion in the ipsilateral DRG. Ryk mRNA levels increased slightly from 1 to 2 weeks, decreased then by 3 weeks post-lesion. These results indicate that Ryk might be involved in peripheral nerve plasticity after injury. This is a novel function apart from its well-known fundamental activity as a receptor mediating axon guidance and outgrowth.

Calcitonin gene-related peptide dynamics in rat dorsal root ganglia and spinal cord following different sciatic nerve injuries

We examined calcitonin gene-related peptide (CGRP) expression dynamics in the dorsal root ganglia (DRGs) and spinal cords of adult rats subjected to one of the following three types of unilateral sciatic nerve injury: crush (SNC), ligation (SNL), or transection combined with subsequent neurorrhaphy (SNT). Following SNC, CGRP immunoreactivity (IR) was increased in ipsilateral primary sensory neurons of L4–L5 DRGs, laminae I–II and spinal motoneurons; an area of CGRP-labeled fibers in ipsilateral laminae III–V was also increased in size following SNC. CGRP up-regulation exhibited a distinct temporospatial pattern and expression levels had returned to baseline levels by the end of the 28-day test period. Similar to SNC, SNT also resulted in an increase of CGRP-IR in these areas, though to a slightly lesser degree in the three latter areas. By contrast SNL, which is associated with complete blockade of axonal transport, induced a sustained decrease in CGRP-IR in primary sensory neurons of L4–L5 DRGs and superficial laminae (I–IIo), as well as in an ipsilateral area occupied by CGRP-labeled fibers. Interestingly, SNL did not affect CGRP-IR in spinal motoneurons, but did result in an accumulation of nerve growth factor (NGF) distal to ligature that was apparent as early as 1 day post-injury and persisted throughout the experimental period. These findings indicate that the nature of peripheral nerve injury has an impact on CGRP expression dynamics and that the response involves target tissues in vivo. Our results have important implications for elucidating the mechanisms of nerve regeneration.

Genetic analysis of neuropathic pain-like behavior following peripheral nerve injury suggests a role of the major histocompatibility complex in development of allodynia

Neuropathic pain is a common consequence of damage to the nervous system. We here report a genetic analysis of development of neuropathic pain-like behaviors after unilateral photochemically-induced ischemic sciatic nerve injury in a panel of inbred rat strains known to display different susceptibility to autoimmune neuroinflammation. Pain behavior was initially characterized in Dark-Agouti (DA; RT1 av1 ), Piebald Virol Glaxo (PVG; RT1 c ), and in the major histocompatibility complex (MHC)-congenic strain PVG- RT1 av1 . All strains developed mechanical hypersensitivity (allodynia) following nerve injury. However, the extent and duration of allodynia varied significantly among the strains, with PVG displaying more severe allodynia compared to DA rats. Interestingly, the response of PVG- RT1 avRT1 was similar to that of DA, suggesting regulation by the MHC locus. This notion was subsequently confirmed in an F2 cohort derived from crossing of the PVG and PVG- RT1 av1 strains, where allodynia was reduced in homozygous or heterozygous carriers of the RT1 av1 allele in comparison to rats homozygous for the RT1 c allele. These results indicate that certain allelic variants of the MHC could influence susceptibility to develop and maintain neuropathic pain-like behavior following peripheral nerve injury in rats.

Absence of Thermal Hyperalgesia in Serotonin Transporter-Deficient Mice

Antidepressants in the treatment of neuropathic pain are thought to partially exert their effect by inhibition of serotonin (5-HT) reuptake and thus activation of central antinociceptive pathways. Mice deficient for the 5-HT transporter (5-HTT-/- mice) are regarded as a model of lifelong treatment with a serotonin reuptake inhibitor. Here we investigated 5-HTT-/- mice and compared their pain-related behavior after a unilateral chronic constrictive sciatic nerve injury (CCI) with that of wild-type littermates. Wild-type mice reproducibly developed ipsilateral thermal hyperalgesia and mechanical allodynia after CCI. 5-HTT-/- mice did not develop thermal hyperalgesia, but showed bilateral mechanical allodynia after the nerve injury. 5-HT levels as measured with HPLC increased after CCI in the injured nerve in both genotypes and decreased in the lumbar spinal cord in wild-type mice. 5-HTT-/- mice had significantly lower 5-HT concentrations than wild-type mice in all tissues investigated. Thus, in 5-HTT-/- mice, reduced 5-HT levels in the injured peripheral nerves correlate with diminished behavioral signs of thermal hyperalgesia, a pain-related symptom caused by peripheral sensitization. In contrast, bilateral mechanical allodynia, a centrally mediated phenomenon, was associated with decreased spinal 5-HT concentrations in 5-HTT-/- mice and may possibly be caused by a lack of spinal inhibition.

Identification and Characterization of Differentially Expressed Genes in Denervated Muscle

Denervation results in a series of changes in skeletal muscle. To elucidate the molecular basis underlying these changes, it is important to identify the profile of altered gene expression in skeletal muscle following nerve injury. In the present study, we have examined the differentially expressed genes in denervated gastrocnemius muscle using RNA fingerprinting by arbitrarily primed PCR. Eight differentially expressed mRNA transcripts have been identified. A bilateral regulatory profile can be observed for the up-regulated genes in both denervated and contralateral control muscle following unilateral sciatic nerve injury. The temporal expression profiles of the denervation-regulated genes in muscle during development, together with their dependency on nerve activity, suggest potential functional roles following nerve injury in vivo. In particular, the identification of two apoptosis-related genes in denervated muscle provides molecular evidence that the apoptotic process is likely to be involved in the intricate changes that lead to muscle atrophy. Our findings not only allow the identification of novel genes, but also suggest possible functions for some known genes in muscle following nerve injury. Taken together, these findings provide important insights into our understanding of the molecular events in denervated muscle and suggest that the differentially expressed genes may play potential roles during muscle denervation and regeneration.

Unilateral sciatic nerve injury stimulates contralateral nerve regeneration.

Axonal outgrowth in tissue cultures was measured to determine whether unilateral peripheral nerve injuries affect contralateral nerve regeneration. The right sciatic nerves of young male Wistar rats were cut at mid-thigh level. Sham operation as a control was limited to the exposure of the nerve without cutting. At day 6 post-surgery, bilateral L5 dorsal root ganglia (DRG) with attached nerve stumps were resected and cultured. Axonal outgrowth from the nerve stump was measured in situ. The contralateral preparations showed longer outgrowths than controls. Therefore the conditioning effect was not merely restricted to the ipsilateral neurons but also affected undamaged sensory neurons of the contralaretal DRG.