Pulsed radiofrequency or anterior neurectomy for anterior cutaneous nerve entrapment syndrome (ACNES) (the PULSE trial): study protocol of a randomized controlled trial.

BACKGROUND: Some patients with chronic abdominal pain suffer from an anterior cutaneous nerve entrapment syndrome (ACNES). This somewhat illusive syndrome is thought to be caused by the entrapment of end branches of the intercostal nerves residing in the abdominal wall. If ACNES is suspected, a local injection of an anesthetic agent may offer relief. If pain is recurrent following multiple-injection therapy, an anterior neurectomy entailing removal of the entrapped nerve endings may be considered. After 1 year, a 70% success rate has been reported. Research on minimally invasive alternative treatments is scarce. Pulsed radiofrequency (PRF) treatment is a relatively new treatment for chronic pain syndromes. An electromagnetic field is applied around the nerve in the hope of leading to pain relief. This randomized controlled trial compares the effect of PRF treatment and neurectomy in patients with ACNES. METHODS: Adult ACNES patients having short-lived success following injections are randomized to PRF or neurectomy. At the 8-week follow-up visit, unsuccessful PRF patients are allowed to cross over to a neurectomy. Primary outcome is pain relief after either therapy. Secondary outcomes include patient satisfaction, quality of life, use of analgesics and unanticipated adverse events. The study is terminated 6 months after receiving the final procedure. DISCUSSION: Since academic literature on minimally invasive techniques is lacking, well-designed trials are needed to optimize results of treatment for ACNES. This is the first large, randomized controlled, proof-of-concept trial comparing two therapy techniques in ACNES patients. The first patient was included in October 2015. The expected trial deadline is December 2017. If effective, PRF may be incorporated into the ACNES treatment algorithm, thus minimizing the number of patients requiring surgery. TRIAL REGISTRATION: Nederlands Trial Register (Dutch Trial Register), NTR5131 ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5131 ). Registered on 15 April 2015.

The Dorsal Root Ganglion as a Therapeutic Target for Chronic Pain.

Chronic neuropathic pain is a widespread problem with negative personal and societal consequences. Despite considerable clinical neuroscience research, the goal of developing effective, reliable, and durable treatments has remained elusive. The critical role played by the dorsal root ganglion (DRG) in the induction and maintenance of chronic pain has been largely overlooked in these efforts, however. It may be that, by targeting this site, robust new options for pain management will be revealed. This review summarizes recent advances in the knowledge base for DRG-targeted treatments for neuropathic pain:• Pharmacological options including the chemical targeting of voltage-dependent calcium channels, transient receptor potential channels, neurotrophin production, potentiation of opioid transduction pathways, and excitatory glutamate receptors.• Ablation or modulation of the DRG via continuous thermal radiofrequency and pulsed radiofrequency treatments.• Implanted electrical neurostimulator technologies.• Interventions involving the modification of DRG cellular function at the genetic level by using viral vectors and gene silencing methods.

Anti-skeletal muscle atrophy effect of Oenothera odorata root extract via reactive oxygen species-dependent signaling pathways in cellular and mouse model.

Skeletal muscle atrophy can be defined as a decrease of muscle volume caused by injury or lack of use. This condition is associated with reactive oxygen species (ROS), resulting in various muscular disorders. We acquired 2D and 3D images using micro-computed tomography in gastrocnemius and soleus muscles of sciatic-denervated mice. We confirmed that sciatic denervation-small animal model reduced muscle volume. However, the intraperitoneal injection of Oenothera odorata root extract (EVP) delayed muscle atrophy compared to a control group. We also investigated the mechanism of muscle atrophy's relationship with ROS. EVP suppressed expression of SOD1, and increased expression of HSP70, in both H2O2-treated C2C12 myoblasts and sciatic-denervated mice. Moreover, EVP regulated apoptotic signals, including caspase-3, Bax, Bcl-2, and ceramide. These results indicate that EVP has a positive effect on reducing the effect of ROS on muscle atrophy.

The efficacy of two electrodes radiofrequency technique: comparison study using a cadaveric interspinous ligament and temperature measurement using egg white.

BACKGROUND: One technique in radiofrequency neurotomies uses 2 electrodes that are simultaneously placed to lie parallel to one another. Comparing lesions on cadaveric interspinous ligament tissue and measuring the temperature change in egg white allows us to accurately measure quantitatively the area of the lesion. METHODS: Fresh cadaver spinal tissue and egg white tissue were used. A series of samples were prepared with the electrodes placed 1 to 7 mm apart. Using radiofrequency, the needle electrodes were heated in sequential or simultaneous order and the distance of the escaped lesion area and temperature were measured. RESULTS: Samples of cadaver interspinous ligament showed sequential heating of the needles limits the placement of the needle electrodes up to 2 mm apart from each other and up to 4 mm apart when heated simultaneously. The temperature at the escaped lesion area decreased according to the distance for egg white. There was a significant difference in temperature at the escaped lesion area up to 6 mm apart and the temperature was above 50 degrees celsius up to 5 mm in simultaneous lesion and 3 mm in the sequential lesion. LIMITATIONS: The limitations of this study include cadaveric experimentation and use of intraspinous ligament rather than medial branch of the dorsal ramus which is difficult to identify. CONCLUSION: Heating the 2 electrodes simultaneously appears to coagulate a wider area and potentially produce better results in less time.

Electrical stimulation promotes motor nerve regeneration selectivity regardless of end-organ connection.

Previous studies have demonstrated that end-organ deprivation after peripheral nerve injury results in targeting of regenerating nerve fibers into inappropriate pathways, which leads to poor functional recovery. Here we studied the effect of electrical stimulation on the regeneration selectivity of motor nerves after peripheral nerve injury and end-organ deprivation. We found that end-organ deprivation reduced regenerating selectivity of motor nerves, total number of regenerating motoneurons, and level of neural trophic factors in the regenerating pathways after nerve injury (p < 0.05). Electrical stimulation successfully promoted motor nerve regeneration selectivity regardless of end-organ connections (p < 0.05). This increased selectivity was accompanied by an increase in the protein level of neural trophic factors in the distal nerve stumps by 3 weeks after nerve injury (p < 0.05). There was a similar increase in the protein level of these neural trophic factors in denervated muscle. However, the RNA level of these factors decreased both in the distal nerves and in the muscle. Despite the promising effect of promoting motor nerve regeneration selectivity, electrical stimulation did not prevent motoneuron loss caused by end-organ deprivation. The present study suggests that end organs contribute to the development of selective motor nerve regeneration by increasing the neurotrophic factors in the regeneration pathways. Electrical stimulation is an efficient strategy to ameliorate the deteriorated regeneration microenvironment caused by end-organ deprivation and to promote motor nerve regeneration selectivity when end-organ connections are deprived.

Effects of chronic electrical stimulation on long-term denervated muscles of the rabbit hind limb.

We investigated the extent to which activity induced by chronic electrical stimulation could restore the mass and contractile function of rabbit tibialis anterior (TA) muscles that had undergone atrophy as a result of prolonged denervation. Denervation was carried out by selectively interrupting the motor nerve branches to the ankle dorsiflexors in one hind limb. Stimulators were implanted, with electrodes on the superficial and deep surfaces of the denervated TA muscle. Ten weeks later, the mass and mid-belly cross-sectional area (CSA) of TA muscles subjected to denervation alone had fallen to approximately 40% of normal. At this stage, stimulators in the other rabbits were activated for 1 h/day to deliver 20-ms rectangular bipolar constant-current pulses of 4 mA amplitude at 20 Hz with a duty cycle of 1s ON/2s OFF, a total of 24,000 impulses/day. The animals were examined after a further 2, 6 or 10 weeks. Stimulation restored the wet weight of the denervated muscles to values not significantly different to those of normal, innervated controls. It increased CSA from 39% to 66% of normal, and there was a commensurate increase in maximum isometric tetanic force from 27% to 50% of normal. Light and electron microscopic examination revealed a marked improvement in the size, packing, and internal organization of the stimulated-denervated muscle fibres, suggestive of an ongoing process of restoration. Excitability, contractile speed, power, and fatigue resistance had not, however, been restored to normal levels after 10 weeks of stimulation. Similar results were found for muscles that had been denervated for 39 weeks and then stimulated for 12 weeks. The study demonstrates worthwhile benefits of long-term electrical stimulation in the treatment of established denervation atrophy.

Deep brain stimulation for pain relief: a meta-analysis.

Deep brain stimulation (DBS) has been used to treat intractable pain for over 50 years. Variations in targets and surgical technique complicate the interpretation of many studies. To better understand its efficacy, we performed a meta-analysis of DBS for pain relief. MEDLINE (1966 to February 2003) and EMBASE (1980 to January 2003) databases were searched using key words deep brain stimulation, sensory thalamus, periventricular gray and pain. Inclusion criteria were based on patient characteristics and protocol clarity. Six studies (between 1977-1997) fitting the criteria were identified. Stimulation sites included the periventricular/periaqueductal grey matter (PVG/PAG), internal capsule (IC), and sensory thalamus (ST). The long-term pain alleviation rate was highest with DBS of the PVG/PAG (79%), or the PVG/PAG plus sensory thalamus/internal capsule (87%). Stimulation of the sensory thalamus alone was less effective (58% long-term success) (p < 0.05). DBS was more effective for nociceptive than deafferentation pain (63% vs 47% long-term success; p < 0.01). Long-term success was attained in over 80% of patients with intractable low back pain (failed back surgery) following successful trial stimulation. Trial stimulation was successful in approximately 50% of those with post-stroke pain, and 58% of patients permanently implanted achieved ongoing pain relief. Higher rates of success were seen with phantom limb pain and neuropathies. We conclude that DBS is frequently effective when used in well-selected patients. Neuroimaging and neuromodulation technology advances complicate the application of these results to modern practice. Ongoing investigations should shed further light on this complex clinical conundrum.

Resection of the sciatic, peroneal, or tibial nerves: assessment of functional status.

BACKGROUND: Lower-extremity tumors are often treated by amputation rather than limb-sparing excision that sacrifices the sciatic nerve or a branch. This study assessed the functional outcome of major nerve sacrifice during limb-sparing resections for lower-extremity soft tissue sarcoma. METHODS: Patients who underwent division of the sciatic, tibial, or peroneal nerve(s) during limb-sparing sarcoma surgery (January 1982 through June 2000) were identified. Eleven surviving patients evaluated their pre- and postoperative functional status by self-administered questionnaire (six sciatic, two tibial, and three peroneal nerve divisions). RESULTS: Eighteen patients (10 male, 8 female; 14-84 years old) had nine primary and nine locally recurrent tumors. Tumors were high (16) or low grade (two). Five patients died of disease and two died of other causes. Median overall survival was 50 months. One of 11 reported increased pain. Eight had new phantom sensations with a median intensity of 4.5 (1 = least; 10 = most). All patients used an ankle brace to walk after a sciatic (four) or peroneal (one) division. Walking ability and distance after surgery was unchanged (nine), improved (one), and worsened (one). Standing improved in 7 of 11 patients. Proprioception in the affected extremity was retained in six. The median postoperative leg functional score was 8 (1 = worst; 10 = best). No patient developed foot ulcers. One patient underwent amputation for recurrence. All patients preferred their status over having an amputation. CONCLUSIONS: Objectively and subjectively, division of the major lower-extremity nerves causes acceptable functional deficits in most patients. Resection of affected sciatic nerve (branches) during limb-sparing tumor surgery is an excellent alternative to amputation.

Altered cortical activation with finger movement after peripheral denervation: comparison of active and passive tasks.

We wished to contrast cortical activation during hand movements in profoundly weak patients with motor neuropathy and in normal controls using a paradigm that is behaviourally matched between the two groups. Previous work has suggested that a passive movement task could be appropriate. Using functional magnetic resonance imaging (fMRI), we first characterised patterns of brain activation during active and passive index finger movements in healthy controls (n=10). Although the relative activation differences were highly variable, there was a trend for the mean number of significantly activated voxels in the primary motor cortex contralateral to the hand moved (CMC) to be lower for the passive than for the active task (40% relative decrease, P=0.09). There was a small posterior shift in the centre of mass of the CMC (mean, 8 mm, P<0.02) and of the ipsilateral sensorimotor cortex (IMC) (mean, 11 mm, P<0.05). No activation with passive movement was found in the patients with severe distal sensory neuropathy (n=2), suggesting that activation with passive movements is dependent on sensory feedback and unlikely to be due to mental imagery alone. In contrast, patients with severe pure motor neuropathies (MN, n=2) showed substantial increases in the volumes of activation compared to controls. The relative increases in numbers of voxels activated above threshold in different regions of interest for both the active (MN/controls: CMC, 2. 1; IMC, 8.1; supplementary motor area [SMA], 5.2) and passive (CMC, 2.6; IMC, 8.0; SMA, 5.1) tasks were similar. These results confirm expansion of cortical representation for finger movement in patients with motor neuropathy and demonstrate central reorganisation as a consequence of the motor nerve loss. An expanded representation for finger movement in the primary motor cortex with peripheral weakness suggests the possibility that the primary motor cortex may encode motor unit activation rather directly.

The role of the chorda tympani nerve in the activation of the rat hypothalamic histaminergic system by leptin.

A possible pathway through which leptin activates the histaminergic system was studied using in vivo microdialysis in rats. Intraperitoneal injection of leptin (1.3 mg/kg) caused a significant increase in hypothalamic histamine release, however, its intracerebroventricular injection (10 microg/rat) did not cause any significant changes in the release. Furthermore, leptin (1.3 mg/kg) had no effect on histamine release in rats whose chorda tympani nerves, a branch of the facial nerve which mediates taste information, were transected bilaterally. These findings indicate that leptin activates the histaminergic system by the peripheral signal inputs via the chorda tympani resulting in the suppression of food intake.

Auditory deprivation modifies biological rhythms in the golden hamster.

To assess to what extent auditory sensory deprivation affects biological rhythmicity, sleep/wakefulness cycle and 24 h rhythm in locomotor activity were examined in golden hamsters after bilateral cochlear lesion. An increase in total sleep time as well as a decrease in wakefulness (W) were associated to an augmented number of W episodes, as well as of slow wave sleep (SWS) and paradoxical sleep (PS) episodes in deaf hamsters. The number of episodes of the three behavioural states and the percent duration of W and SWS increased significantly during the light phase of daily photoperiod only. Lower amplitudes of locomotor activity rhythm and a different phase angle as far as light off were found in deaf hamsters kept either under light-dark photoperiod or in constant darkness. Period of locomotor activity remained unchanged after cochlear lesions. The results indicate that auditory deprivation disturbs photic synchronization of rhythms with little effect on the clock timing mechanism itself.

The influence of pallidal deep brain stimulation on striatal dopaminergic metabolism in the rat.

Deep brain stimulation of the globus pallidus internus has been recently shown to alleviate parkinsonian symptoms and levodopa-induced dyskinesias. However, its exact mechanisms of action are unclear. Pallidal neurones are connected via various pathways to the dopaminergic nigrostriatal system. In the present study we investigated the hypothesis that deep brain stimulation of the entopeduncular nucleus (corresponds to the human internal pallidum) affects striatal dopaminergic metabolism in naive and 6-hydroxydopamine (6-OHDA) lesioned rats using microdialysis. Our results show that stimulation of the entopeduncular nucleus does not significantly affect striatal dopamine metabolism (of dopamine, 3, 4-dihdroxyphenylacetic acid and homovanillic acid) in naive and 6-OHDA-lesioned animals. They contrast with our previous observations that deep brain stimulation of the subthalamic nucleus increases striatal dopamine metabolism suggesting differential effects of these nuclei on striatal dopamine metabolism.

Hormonal regulation of hippocampal spine synapse density involves subcortical mediation.

It is well established that estrogen has positive effects on the density of pyramidal cell spines in the hippocampal CA1 subfield. This study explored whether afferent connections of the hippocampus that come from estrogen-sensitive subcortical structures, including the septal complex, median raphe and supramammillary area, play a role in this estrogen-induced hippocampal synaptic plasticity. These particular subcortical structures have major influences on hippocampal activity, including theta rhythm and long-term potentiation. The latter also promotes the formation of new synapses. All of the rats were ovariectomized; the fimbria/fornix, which contains the majority of subcortical efferents to the hippocampus, was transected unilaterally in each, and half of the animals received estrogen replacement. Using unbiased electron microscopic stereological methods, the CA1 pyramidal cell spine synapse density was calculated. In the estrogen-treated rats, contralateral to the fimbria/fornix transection, the spine density of CA1 pyramidal cells increased dramatically, compared to the spine density values of both the ipsilateral and contralateral hippocampi of non-estrogen-treated animals and to that of the ipsilateral hippocampus of the estrogen replaced rats. These observations indicate that fimbria/fornix transection itself does not considerably influence CA1 area pyramidal cell spine density and, most importantly, that the estrogenic effect on hippocampal morphology, in addition to directly affecting the hippocampus, involves subcortical mediation.

The effect of callosotomy on testicular steroidogenesis in hemiorchidectomized rats: a pituitary-independent regulatory mechanism.

In recent years, increasing number of data indicate that cerebral structures exert a direct, pituitary-independent, neural regulatory action on the endocrine glands. In addition, both experimental and clinical observations indicate functional asymmetry of the control system. Therefore, the objective of the present study was to study the effect of callosotomy on testicular steroidogenesis and serum gonadotrop concentrations in rats subjected to left- or right-sided orchidectomy. In animals underwent callosotomy plus left-sided orchidectomy the basal testosterone secretion in vitro of the remaining (right) testis was significantly higher than that of intact controls, and of rats subjected to sham surgery plus left orchidectomy. In contrast, either sham operation or callosotomy plus right-sided orchidectomy did not interfere with testicular steroidogenesis. Sham surgery or callosotomy plus left orchidectomy induced a significant rise in serum follicle-stimulating hormone concentration while right orchidectomy combined either with sham surgery or callosotomy did not alter this parameter. There was no statistically significant difference between experimental groups in serum testosterone and luteinizing hormone concentrations. The results indicate the involvement of the corpus callosum in a pituitary-independent neural control of testicular steroidogenesis. The data further suggest a different response in steroidogenesis of the left and the right testis following hemicastration and callosotomy.

Cardiovascular responses in anticipation of changes in posture and locomotion.

Measurements were made in 29 adult baboons that were housed in social groups, allowing the occurrence of the full range of species-specific behavioral interactions. The cardiovascular variables measured included blood pressure, heart rate, renal blood flow, lower limb blood flow, and occasionally mesenteric blood flow. The data were telemetered from backpacks worn by the animals and were recorded in analogue form on a polygraph, digitally on a computer and were also recorded on the audio channels of videotape being made of the behavior and social interactions of the baboons. The video and the computer recordings were synchronized by a timing system that made it possible to relate the cardiovascular responses to the behavioral responses. A numerically based behavioral code was developed that allowed the categorization of the totality of the behavior, including postural and locomotor changes. Comparisons between baseline cardiovascular values and those occurring 1 s before the initiation of a movement or posture change gave no evidence of anticipatory cardiovascular responses unless the movement was associated with behavior that included emotional content. Hypothalamic perifornical lesions reduced or eliminated these anticipatory changes.

Inhibition of nitric oxide synthase prevents alpha 7 nicotinic receptor-mediated restoration of inhibitory auditory gating in rat hippocampus.

The hippocampus rapidly inhibits its response to repetitive auditory stimulation, an example of an auditory sensory gating mechanism involved in human psychopathology. The neuronal basis of this inhibitory gating mechanism has been investigated in rats. Activation of the alpha 7 nicotinic receptor is required. alpha 7 nicotinic receptor activation also releases nitric oxide in the hippocampus and blockade of nitric oxide synthase reduces inhibitory gating of auditory response. There has not been a direct demonstration that blockade of nitric oxide synthase specifically prevents alpha 7 nicotinic receptor activation of the inhibition of auditory response. Therefore, the goal of the present study was to determine whether this functional effect of alpha 7 receptor activation requires release of nitric oxide. Lesions of the fimbria-fornix disrupt auditory gating by preventing cholinergic stimulation of the hippocampus. Following recovery from this surgery, rats were administered 3-(2,4-dimethoxybenzylidene) anabaseine (DMXB-A; 10 mg/kg, sc), an agonist at the alpha 7 receptor. DMXB-A restored auditory gating in the fimbria-fornix-lesioned rats, indicating that activation of the alpha 7 nicotinic receptor alone is sufficient to restore auditory gating following lesions of the fimbria-fornix. However, intracerebroventricular infusion of N(omega)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, blocked the DMXB-A-mediated restoration of auditory gating; infusion of the inactive D-enantiomer did not. Restoration of auditory gating by DMXB-A in the fimbria-fornix-lesioned rats was blocked by intracerebroventricular infusion of alpha-bungarotoxin, but not by mecamylamine or dihydro-beta-erythroidine. Together, these data support the hypothesis that nitric oxide mediates alpha 7 nicotinic receptor activation of gating of auditory response in rat hippocampus.

Temporal progression of kainic acid induced neuronal and myelin degeneration in the rat forebrain.

The excitatory amino acid glutamate has been implicated in the neurodegeneration associated with several different central nervous system diseases. Treatment with kainic acid (KA), a glutamate analog known to activate the AMPA/KA subtype of glutamate receptor, has been widely used as a model of epilepsy. Long term temporal studies of its neuropathological effects, however, are lacking. In this study, two techniques were used to directly visualize and characterize the neuropathology that occurred over a 2-month period following KA-induced status epilepticus in adult female Sprague-Dawley rats. Post-injection survival was 2, 4, 8 h, 2 days, 2 weeks, or 2 months. Labeling with Fluoro-Jade B (FJB), a fluorescent green dye that labels the cell body, dendrites, axons and axon terminals of degenerating neurons, was observed within the cortex, hippocampus, thalamus, basal ganglia, and amygdala by 4 h post-treatment. The highest level of labeling was seen in the piriform cortex, hippocampus, and thalamus. Myelin changes in the rat forebrain following KA treatment were also examined using the myelin-specific Black-Gold (BG) stain. Varicose myelinated fibers were observed in the same regions as FJB positive neurons, although these changes were evident by the 2-h survival time-point. Both stains showed a temporal progression of brain damage throughout the affected areas. By 2 months post-treatment, few degenerating neurons could be detected and abnormal myelin was absent in most regions. As myelin changes can be seen prior to neuronal degeneration, and oligodendrocytes express functional AMPA/kainate-type glutamate receptors, the neurodegeneration and myelin pathologies may occur as independent events. Thus, researchers should consider the temporal and multiple effects of kainic acid to optimize conditions for their endpoint of interest when designing experiments.

Altered gene expression in steroid-treated denervated muscle.

In rats treated with high-dose corticosteroids, skeletal muscle that is denervated in vivo (steroid-denervated) develops electrical inexcitability similar to that seen in patients with acute quadriplegic myopathy. To determine whether changes in muscle gene transcription might underlie inexcitability of steroid-denervated muscle we performed RNase protection assays to quantitate adult (SkM1) and embryonic (SkM2) sodium channel isoforms and chloride channel (CLC-1) mRNA levels in control, denervated, steroid-innervated, and steroid-denervated skeletal muscle. While SkM1 mRNA levels were relatively unaffected by denervation or steroid treatment, SkM2 mRNA levels were increased by both. These effects were synergistic and high levels of SkM2 mRNA were expressed in denervated muscle exposed to corticosteroids. Skeletal muscle CLC-1 mRNA levels were decreased by denervation. To better understand the marked upregulation of SkM2 in steroid-denervated muscle we examined changes in myogenin and glucocorticoid receptor mRNA levels. However, changes in these mRNA levels cannot account for the upregulation of SkM2 in steroid-denervated muscle.

Chronic penile denervation in the rat: effect on cavernous tissue morphology and function.

We evaluated the effects of chronic penile denervation on cavernous tissue morphology and function in 36 Sprague-Dawley rats. At age seven weeks, 18 animals underwent bilateral cavernous nerve neurectomy: 18 animals underwent sham operation as a control. A functional, biochemical and morphological assessment of the rats' penises was performed at 4 months. In denervated rats, intracavernous pressure failed to rise with electrostimulation of the pelvic plexus. However, a normal rise in pressure was found with direct intracavernous injection of sodium nitroprusside and papaverine. Sodium dodecylsulfate polyacrylamide (SDS) gel electrophoresis of the penile homogenate showed subtle differences between denervated and control animals. Based upon the histological findings there was no difference in staining of the cavernous tissue for acetylcholinesterase- and catecholamine-positive nerve fibers between experimental and control animals, since the innervation density was not quantified and the number of fibers was not counted. We conclude that chronic cavernous nerve neurectomy does not cause significant morphological or functional changes to the penile erectile tissue of rats.

Autotomy following sciatic and saphenous nerve sections: sparing of the medial toes after treatment of the sciatic nerve with capsaicin.

Autotomy, or self-mutilation of the foot following sciatic and saphenous nerve lesions, was examined in rats after pretreatment of the sciatic nerve with capsaicin. This pretreatment produced an alteration in autotomy behavior which resulted in the sparing of the medial side of the foot. The effect occurred following a long (12-week) pretreatment-test interval, but not after shorter (1- and 4-week) intervals. The effect also depended on the successive transecting of the saphenous and sciatic nerves. Sparing of the medial side of the foot occurred only when the saphenous nerve was transected at the time of the sciatic nerve treatment with capsaicin. Because the side of the foot innervated by the saphenous nerve was spared by treating the sciatic nerve with capsaicin, we suggest that capsaicin alters the course of autotomy by preventing collateral innervation of the saphenous region by the intact sciatic nerve during the pretreatment-test interval. The fact that this occurs only after a 12-week interval suggests that capsaicin's effect on collateral innervation is a gradual process that requires a long time to develop.