Pattern Of Reinnervation Research Articles

Patterns of Target Tissue Reinnervation and Trophic Factor Expression after Nerve Grafting

Reinnervation of target tissues determines functional outcomes after nerve grafting, which is important in traumatic injury caused by accidents or consequences resulting from surgical removal of tumors. Previous studies documented the influences of nerve repair mainly based on nerve morphometry but rarely compared the final outcomes according to target reinnervation patterns by nerve fibers of different categories. In a mouse model of nerve grafting, the authors analyzed the innervation indexes of different target tissues after transection-reimplantation on the sciatic nerve, which were defined as a parameter on the operated side normalized to that on the control side. Muscle reinnervation appeared to be the best compared with skin reinnervation (p < 0.0001) and sweat gland reinnervation (p < 0.0001) at postoperative month 3. The sudomotor reinnervation was relatively higher than the cutaneous reinnervation (p = 0.014). The abundance of trophin transcripts for brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and neurotrophin 3 (NT3) was higher in plantar muscles on the operated side than those on the control side. In contrast, transcripts of BDNF, GDNF, nerve growth factor, and NT3 were all similar in the footpad skin between the operated and control sides. The results suggested that, compared with the skin, muscles achieved the best reinnervation after nerve grafting, which was related to higher expression of BDNF, GDNF, and NT3 in muscles than in the skin.

Losing Your Voice: Etiologies and Imaging Features of Vocal Fold Paralysis

Neurogenic compromise of vocal fold function exists along a continuum encompassing vocal cord hypomobility (paresis) to vocal fold immobility (paralysis) with varying degrees and patterns of reinnervation. Vocal fold paralysis (VFP) may result from injury to the vagus or the recurrent laryngeal nerves anywhere along their course from the brainstem to the larynx. In this article, we review the anatomy of the vagus and recurrent laryngeal nerves and examine the various etiologies of VFP. Selected cases are presented with discussion of key imaging features of VFP including radiologic findings specific to central vagal neuropathy and peripheral recurrent nerve paralysis.

Re-innervation patterns by peptidergic Substance-P, non-peptidergic P2X3, and myelinated NF-200 nerve fibers in epidermis and dermis of rats with neuropathic pain

Nerve endings in the epidermis, termed nociceptors, conduct information on noxious stimuli to the central nervous system. The precise role of epidermal nerve fibers in neuropathic pain is however still controversial. Here, we have investigated the re-innervation patterns of epidermal and dermal nerve fibers in a rat neuropathic pain model. After applying the spared nerve injury (SNI) model, we determined the mechanical and thermal withdrawal thresholds in the uninjured lateral (sural) and medial (saphenous) areas of the affected hind paw and investigated the innervations patterns of Substance P (SubP), Neurofilament-200 (NF-200) and P2X3-immunoreactive (IR) nerve fibers in the epidermis and dermis. We found a significant loss in the density of peptidergic (Sub P and NF-200) and non-peptidergic (P2X3) nerve fibers in the center area of the foot sole at 2weeks postoperatively (PO). The densities of Sub P-IR fibers in the epidermis and upper dermis, and the density of P2X3-IR fibers in the upper dermis were significantly increased at 10weeks PO as compared to 2weeks PO, but were still significantly lower than the densities in controls. However, the density of NF-200-IR fibers in the center area reached control levels at 10weeks PO. No changes were found in the densities of any of the fibers in the medial and lateral parts of the foot sole. The present results suggest that after peripheral nerve injury, specific nerve fibers have different re-innervation patterns in the epidermis and dermis and that they might be involved in the development of neuropathic pain.

Reduced removal of synaptic terminals from axotomized spinal motoneurons in the absence of complement C3

Complement proteins C1q and C3 play a critical role in synaptic elimination during development. Axotomy of spinal motoneurons triggers removal of synaptic terminals from the cell surface of motoneurons by largely unknown mechanisms. We therefore hypothesized that the complement system is involved also in synaptic stripping of injured motoneurons. In the sciatic motor pool of wild type (WT) mice, the immunoreactivity (IR) for both C1q and C3 was increased after sciatic nerve transection (SNT). Mice deficient in C3 (C3−/−) showed a reduced loss of synaptic terminals from injured motoneurons at one week after SNT, as assessed by immunoreactivity for synaptic markers and electron microscopy. In particular, the removal of putative inhibitory terminals, immunopositive for vesicular inhibitory amino acid transporter (VIAAT) and ultrastructurally identified as type F synapses, was reduced in C3−/− mice. In contrast, lesion-induced removal of nerve terminals in C1q−/− mice appeared similar to WT mice. Growth associated protein (GAP)-43 mRNA expression in lesioned motoneurons increased much more in C3−/− compared to WT mice after SNT. After sciatic nerve crush (SNC), the C3−/− mice showed a faster functional recovery, assessed as grip strength, compared to WT mice. No differences were detected regarding nerve inflammation at the site of injury or pattern of muscle reinnervation. These data indicate that a non-classical pathway of complement activation is involved in axotomy-induced adult synapse removal, and that its inhibition promotes functional recovery.

The reinnervation pattern of wounds and scars after treatment with transforming growth factor β isoforms

Wounds deprived of innervation fail to heal normally, and hypertrophic scars may be abnormally innervated. Manipulation of wounds alters the subsequent degree of scarring, and isoforms of transforming growth factor beta (TGFβ) are well established in this role, whilst TGFβ3 is undergoing clinical trials as an antiscarring agent for clinical use. It is unclear if treated wounds show changes in their innervation patterns as they mature into scars. Mice underwent 1cm(2) full thickness skin excisions which were treated with TGFβ1 or TGFβ3. Wounds were harvested between 5 and 84 days (n=6 at each time point). Sections underwent histological scar assessment and immunohistochemical staining for protein gene product 9.5 (PGP9.5), a pan-neuronal marker, and the sensory neuropeptides calcitonin gene related peptide (CGRP) and substance P (SP). There was no difference in the reinnervation pattern between the peripheral and central parts of the wounds. Wounds treated with TGFβ3 healed with dermal collagen organised more like normal skin, whereas TGFβ1 treated wounds had abnormally orientated collagen within the scar compared to control treated wounds. Nerve fibre growth into the wounds followed a similar pattern in control and treated wounds, with only one significant difference during the healing process- at 42 days, the density of nerve fibres immunostained with PGP9.5 within the scar was greater than in control wounds. By 84 days, the density of PGP9.5, CGRP and SP immunopositive fibres were similar in control wounds and those treated with TGFβ isoforms. Changes in reinnervation patterns of wounds treated with TGFβ isoforms were only slightly different from those of control wounds, and by 84 days, the patterns were similar.

Electrophysiologic Evidence of Spinal Accessory Neuropathy in Patients With Cervical Myofascial Pain Syndrome

Chang C-W, Chang K-Y, Chen Y-R, Kuo P-L. Electrophysiologic evidence of spinal accessory neuropathy in patients with cervical myofascial pain syndrome. Objective To evaluate whether or not spinal accessory neuropathy exists in patients with cervical myofascial pain syndrome (MFPS). Design Prospective study. Setting A neurophysiologic laboratory in a university hospital. Participants Patients with cervical MFPS (n=25) and healthy controls (n=20). Interventions Not applicable. Main Outcome Measures We performed nerve conduction studies (NCSs) in bilateral spinal accessory nerves, and electromyography and stimulated single-fiber electromyography in the trapezius muscles of all patients and controls. Parameters including nerve conduction velocities (NCVs), amplitudes and areas of compound muscle action potentials (CMAPs), and mean consecutive differences (MCDs) in single-fiber electromyography were measured, analyzed, and compared with the disease durations of the patients. Results Spinal accessory NCSs showed normative NCVs but with prominently reduced CMAP amplitude in the patients with cervical MFPS, which is recognized as an axonal neuropathy of the spinal accessory nerves. Electromyography showed prominent evidence of denervation and reinnervation patterns in 48% of the MFPS patients. The abnormal MCDs in single-fiber electromyography indicated a synaptic delay of motor endplates in the motor units, and may signify evolving instability of neuromuscular transmission in the spinal accessory nerves innervating trapezius muscles of the patients. Conclusions This study demonstrates electrophysiologic evidence of neuroaxonal degeneration and neuromuscular transmission disorder in a significant proportion of patients with cervical MFPS. We suggest that spinal accessory neuropathy may be associated with cervical MFPS.

The reinnervation and revascularisation pattern of scarless murine fetal wounds

Fetal wounds can heal without scarring. There is evidence that the sensory nervous system plays a role in mediating inflammation and healing, and that the reinnervation pattern of adult wounds differs from that of unwounded skin. Ectoderm is required for development of the cutaneous nerve plexus in early gestation. It was hypothesised that scarless fetal wounds might completely regenerate their neural and vascular architecture. Wounds were made on mouse fetuses at embryonic day 16.5 of a 19.5-day gestation, which healed without visible scars. Immunohistochemical analysis of wound sites was performed to assess reinnervation, using antibodies to the pan neuronal marker PGP9.5 as well as to the neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP). Staining for the endothelial marker von Willebrand factor (VWF) allowed comparison of reinnervation and revascularisation. Wounds were harvested at timepoints from day 1 after wounding to postnatal day 6. Quantification of wound reinnervation and revascularisation was performed for timepoints up to 6 days post-wounding. Hypervascularisation of the wounds occurred within 24 h, and blood vessel density within the wounds remained significantly elevated until postnatal day 2 (4 days post- wounding), after which VWF immunoreactivity was similar between wound and control groups. Wound nerve density returned to a level similar to that of unwounded skin within 48 h of wounding, and PGP9.5 immunoreactive nerve fibre density remained similar to control skin thereafter. CGRP and SP immunoreactivity followed a similar pattern to that of PGP9.5, although wound levels did not return to those of control skin until postnatal day 1. Scarless fetal wounds appeared to regenerate their nerve and blood vessel microanatomy perfectly after a period of hypervascularisation.

The reinnervation and revascularization of wounds is temporarily altered after treatment with interleukin 10

Denervated wounds fail to heal normally, and hypertrophic scars are abnormally innervated. Wounds can be manipulated with cytokines to reduce subsequent scarring. Wounds treated with the antiscarring cytokine interleukin 10 (IL10) were investigated to assess if the treatment alterered patterns of reinnervation and revascularization as the wounds matured into scars. Thirty CD1 mice underwent intradermal injection of 100 μL phosphate-buffered saline (PBS) containing 125 ng IL10 or placebo at the margins of 1 cm(2) full thickness dorsal skin excisions at the time of wounding and at 24 hours after wounding. Wounds were not dressed. Six IL10-treated and six control were harvested days 7, 14, 21, 42 and 84 postoperatively. Sections underwent histological scar assessment along with immunohistochemical staining for protein gene product 9.5 (PGP9.5), a pan-neuronal marker, and the sensory neuropeptides calcitonin gene related peptide (CGRP) and substance P (SP). The endothelial marker von Willebrand factor (VWF) was used to allow co-localization and quantification of blood vessels. Quantitative analysis was performed on the periphery and center of wounds. Wounds treated with IL10 healed with dermal collagen organized into a pattern more closely resembling normal skin than control wounds. IL10 changed the pattern of CGRP reinnervation during the healing process, but at 84 days, the density levels of all nerve fiber types were similar to controls. Wounds treated with IL10 were more vascular than untreated wounds during healing, but by 84 days, VWF density was that of unwounded skin.

Dobutamine Stress Echocardiography in Heart Transplant Recipients' Evaluation: The Role of Reinnervation

Introduction Orthotopic heart transplantation renders the recipient denervated. This remodeling of the intrinsic cardiac nervous system should be taken in account during functional evaluation for allograft coronary artery disease. Dobutamine stress echocardiography (DSE) has been used to detect patients at greater risk. The aim of this study was to determine whether patients with various autonomic response levels, and supposed reinnervation patterns, show the same response to DSE. Methods We studied 20 patients who had survived more than 5 years after orthotopic heart transplantation. All patients underwent a Holter evaluation. We considered patients with low variability to be those with less than a 40-bpm variation from the lowest to highest heart rate, so-called “noninnenervated” (group NI). Patients who had 40-bpm or more variation were considered to show high variability and called “reinnervated” (group RI). After that, all patients performed an ergometric test and DSE. Results Groups were defined as NI ( n = 9) and RI ( n = 11). Ergometric tests confirmed this response with NI patients showing less variability when compared to RI patients ( P = .0401). During DSE, patients showed similar median heart rate responses according to the dobutamine dose. Spearmen correlation showed r = 1.0 ( P = .016). Conclusions DES was effective to reach higher heart rates, probably related to catecholamine infusion. These findings may justify a better response when evaluating cardiac allograft vasculopathy in heart transplant patients.

Mouth Movement Disturbance as a Sequela of Bilateral Bell's Palsy

Bell's palsy rarely recurs or arises bilaterally. We describe unique oral motor sequelae that manifest with bilateral facial palsy. Two rare patients with alternating bilateral Bell's palsy experienced compromised mouth movement, affecting eating, speaking, and air exchange, and reduced quality of life. Rehabilitation programs. Electromyography and electroneuronography. On electromyography study, little activity of the orbicularis oris muscle was seen in any mouth or eye movement in Case 1. In Case 2, the electromyography activity of the depressor anguli oris and depressor labii inferioris muscles was stronger than that of the orbicularis oris muscle. The 2 cases demonstrated different patterns of recovery after the same subsequent treatment. Different patterns of reinnervation occur in bilateral Bell's palsy. Mouth movement disturbances after bilateral Bell's palsy are most disabling when incomplete reinnervation (as suggested by electroneuronography) of the orbicularis oris muscle occurs. Misdirection of regenerating nerve fibers produces lesser levels of oral motor impairment.

Re-innervation pattern of the ‘neovagina’ created from the bladder flap in patients with Mayer-Rokitanski-Kistner-Hauser syndrome: An immunochemical study

Background. Cystovaginoplasty (CVP) is a method of vaginal reconstruction in women with Mayer-Rokitansky-Kistner-Hauser Syndrome (MRKHS). The neo-vagina allows normal sexual intercourses, but after CVP, the sexual life of patients with MRKHS does not differ significantly from normal females. Therefore, we decided to elucidate the pattern of sensory re-innervation of the bladder flap used for the surgery.Methods. Biopsies were taken from vaginal vestibule and urinary bladder during the CVP and 1 year later in four patients with MRKHS. The following neurotransmitters were studied calcitonin gene-related peptide (CGRP), galanin (GAL), vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP).Results. CGRP and PACAP nerve fibres were sparse under the urothelium and in submucosal layer of the neovagina, they were more numerous around blood vessels and in the vicinity of smooth muscles. This was similar to the pattern observed in the urinary bladder. VIP- and GAL-positive nerve fibres were most numerous in the submucosa around blood vessels and in smooth muscle bundles of neovagina. They were distinctly less numerous beneath the epithelium. This innervation pattern mimicked that seen in normal vagina and in vaginal vestibule of patients with MRKHS.Conclusions. Our findings demonstrate considerable nervous system plasticity in the bladder flap. Distribution of presumably sensory CGRP and PACAP immunoreactive nerve fibers was similar to the pattern observed within the intact bladder wall, and VIP or GAL immunoreactive nerve fibers (vasomotor functions) were distributed in a manner similar to that observed in the intact vaginal wall.

Skeletal muscle involvement in enthesopathy of the lateral epicondyle of the humerus (so-called tennis elbow)

Muscle specimens from the origin of the m. extensor carpi radialis brevis, were obtained from 53 patients suffering from chronic enthesopathy of the lateral epicondyle of humerus (EELH). Frank neurogenic atrophy as well as disuse atrophy were caused by radicular irritation due to the cervicobrachial syndrome. The borderline and/or reinnervation patterns of the muscle lesion may be due to the compression neuropathy of the peripheral branches of the radial nerve or may reflect adaptation of the muscle to the chronic nociceptive stimulation in sense of chronic reflex atrophy of the muscle. The elbow joint, and especially the humeroradial joint in cases of EELH represents a functional unit. Any damage to any part leads to secondary reparative and adaptive changes in other structures including the muscle.

Manually-stimulated recovery of motor function after facial nerve injury requires intact sensory input

We have recently shown in rat that daily manual stimulation (MS) of vibrissal muscles promotes recovery of whisking and reduces polyinnervation of muscle fibers following repair of the facial nerve (facial–facial anastomosis, FFA). Here, we examined whether these positive effects were: (1) correlated with alterations of the afferent connections of regenerated facial motoneurons, and (2) whether they were achieved by enhanced sensory input through the intact trigeminal nerve. First, we quantified the extent of total synaptic input to motoneurons in the facial nucleus using synaptophysin immunocytochemistry following FFA with and without subsequent MS. We found that, without MS, this input was reduced compared to intact animals. The number of synaptophysin-positive terminals returned to normal values following MS. Thus, MS appears to counteract the deafferentation of regenerated facial motoneurons. Second, we performed FFA and, in addition, eliminated the trigeminal sensory input to facial motoneurons by extirpation of the ipsilateral infraorbital nerve (IONex). In this paradigm, without MS, vibrissal motor performance and pattern of end-plate reinnervation were as aberrant as after FFA without MS. MS did not influence the reinnervation pattern after IONex and functional recovery was even worse than after IONex without MS. Thus, when the sensory system is intact, MS restores normal vibrissal function and reduces the degree of polyinnervation. When afferent inputs are abolished, these effects are eliminated or even reversed. We conclude that rehabilitation strategies must be carefully designed to take into account the extent of motor and/or sensory damage.

Neuromuscular Features in the Camera-Marugo-Cohen Syndrome

We describe the case of a 24-year-old Japanese man suffering from obesity, mental retardation, muscle weakness, camptodactyly, syndactyly, and a urinary tract cleft. His muscle weakness, which was slightly distally dominant in the extremities, was almost static and showed slow progression for several years. He had normal blood chromosomes (46, XY) and showed normal levels of sex hormones. A needle electromyographic examination of the upper- and lower-limb muscles revealed a reinnervation pattern with large-amplitude, long-duration motor unit potentials. A muscle biopsy also showed denervation and reinnervation patterns, with small-group atrophy and type grouping, with numerous small, angulated fibers. Our findings suggest that these neuromuscular features of the Camera-Marugo-Cohen syndrome are caused by neurogenic changes rather than myogenic changes.

Regeneration of Reinnervated Rat Soleus Muscle Is Accompanied by Fiber Transition Toward a Faster Phenotype

The functional recovery of skeletal muscles after peripheral nerve transection and microsurgical repair is generally incomplete. Several reinnervation abnormalities have been described even after nerve reconstruction surgery. Less is known, however, about the regenerative capacity of reinnervated muscles. Previously, we detected remarkable morphological and motor endplate alterations after inducing muscle necrosis and subsequent regeneration in the reinnervated rat soleus muscle. In the present study, we comparatively analyzed the morphometric properties of different fiber populations, as well as the expression pattern of myosin heavy chain isoforms at both immunohistochemical and mRNA levels in reinnervated versus reinnervated-regenerated muscles. A dramatic slow-to-fast fiber type transition was found in reinnervated soleus, and a further change toward the fast phenotype was observed in reinnervated-regenerated muscles. These findings suggest that the (fast) pattern of reinnervation plays a dominant role in the specification of fiber phenotype during regeneration, which can contribute to the long-lasting functional impairment of the reinnervated muscle. Moreover, because the fast II fibers (and selectively, a certain population of the fast IIB fibers) showed better recovery than did the slow type I fibers, the faster phenotype of the reinnervated-regenerated muscle seems to be actively maintained by selective yet undefined cues.

Local stabilization of microtubule assembly improves recovery of facial nerve function after repair

Within a recent study on the recovery of vibrissae motor performance after facial nerve repair in blind (strain SD/RCS) and sighted (strain SD) rats, we found that, despite persisting myotopic disorganization in the facial nucleus, the blind animals fully restored vibrissal whisking. Searching for the morphological substrates of this improved recovery, we compared the amount of cytoskeletal proteins in the leading edge of elongating axons between both strains. Since our results showed an enhanced expression of neuronal class III β-tubulin in the blind rats, we wondered whether this was due to an increased synthesis or to a delayed turnover of microtubules. In the present report, we approached this question applying established pharmacological agents to the transected buccal branch of the facial nerve in sighted Wistar rats perturbing either microtubule assembly towards stabilization (enhanced polymerization with 10 μg/ml taxol) or towards increased synthesis (challenged by destabilization with 100 μg/ml nocodazole and 20 μg/ml vinblastine). Evaluation of the effect(s) 2 months later included estimation of (i) vibrissae motor performance by video-based motion analysis, (ii) the degree of collateral axonal branching by double retrograde neuronal labeling with crystals of Fluoro-Gold and DiI and (iii) the pattern of motor end-plate reinnervation (proportions of mono- and poly-reinnervated) in the largest extrinsic vibrissal muscle, the m. levator labii superioris. We found that only stabilization of microtubules with 10 μg/ml taxol reduced intramuscular axonal sprouting and polyinnervation of the motor end-plates, which was accompanied by improved restoration of function.

Innervation of Tissue-Engineered Corneal Implants in a Porcine Model: A 1-Year In Vivo Confocal Microscopy Study

To examine the pattern of nerve regeneration within tissue-engineered corneal substitutes grafted into host porcine corneas over a 1-year postoperative period. Biodegradable corneal substitutes from cross-linked collagen were implanted into the left eyes of 12 pigs by deep lamellar keratoplasty. Regeneration of severed nerves into the central implant region was investigated with in vivo confocal microscopy. Both implant-recipient and control (right) eyes were examined before surgery and 2, 6, 10, and 12 months after surgery, to quantify the number, density, diameter, and branching of nerve fiber bundles at various corneal depths. Transmission electron microscopy was used to confirm the presence of nerve bundles. Two months after surgery, corneal nerve ingrowth was observed within the deep anterior stroma, with a number and density of regenerated nerves significantly higher than in nonsurgical control eyes (P < 0.01). Nerves within the superficial anterior stroma regenerated by 6 to 10 months after surgery, and the first subbasal epithelial nerves were seen 10 months after surgery. After 1 year, subbasal nerve density recovered to preoperative levels. Nerve fibers in the deep anterior stroma remained significantly thinner relative to control eyes after 1 year (P < 0.001), where both superficial anterior and subbasal nerve diameter did not change relative to control eyes. The pattern of reinnervation within tissue-engineered corneal substitutes has been quantified in vivo. Innervation proceeded rapidly in the deep anterior stroma, followed by repopulation of more superficial regions. One year after surgery, nerve density within the tissue-engineered cornea increased or remained unchanged relative to controls in all corneal regions examined.

Reply to Kreier and Buijs: no sympathy for the claim of parasympathetic innervation of white adipose tissue

to the editor: Kreier and Buijs ([16][1]) have questioned our work ([14][2]) demonstrating the lack of parasympathetic nervous system (PSNS) innervation of white adipose tissue (WAT) in laboratory rats and mice, as well as in Siberian hamsters. We appreciate the opportunity to clarify and extend our

Vocal fold paresis: evidence and controversies

To present and assess the current state of knowledge regarding vocal fold paresis. Neurogenic compromise of vocal fold function exists along a continuum encompassing partial denervation (paresis), complete denervation (paralysis), and variable degrees and patterns of reinnervation. Not abundantly recognized clinically until recently, paresis typically presents with symptoms of glottic insufficiency. As a result of preserved vocal fold mobility, paresis can be difficult to diagnose and to distinguish from innocent vocal fold asymmetry. Laryngoscopy alone has proved an unreliable means of diagnosis, and laryngeal electromyography, although not immune to error itself, is often helpful. Treatment consists of medialization procedures that do not compromise remaining nerve function. Significant disagreement exists regarding the incidence, causes and relationship to other pathologies. In the absence of evidence, natural history must be inferred. Vocal fold paresis is probably a significant source of vocal disability, especially among cases that have eluded straightforward diagnosis. An accurate assessment of its clinical impact, patterns of dysfunction, natural history and relationship to other pathologies depends on diagnostic rigor and accuracy and is still evolving.

Effects of decompression on neuropathic pain behaviors and skin reinnervation in chronic constriction injury

Decompression is an important therapeutic strategy to relieve neuropathic pain clinically; there is, however, lack of animal models to study its temporal course of neuropathic pain behaviors and its influence on nerve regeneration to sensory targets. To address these issues, we established a model of decompression on rats with chronic constriction injury (CCI) and investigated the effect on skin reinnervation. Animals were divided into a decompression group, in which the ligatures were removed, and a CCI group, in which the ligatures remained at postoperative week 4 (POW 4). At this time point, the skin innervation indexes of protein gene product 9.5 (PGP 9.5), substance P (SP), and calcitonin gene-related peptide (CGRP) were reduced in both groups to similar degrees. Beginning from POW 6, the decompression group exhibited significant reductions of thermal hyperalgesia and mechanical allodynia compared to the CCI group ( p < 0.001). At POW 8, neuropathic pain behaviors had completely disappeared in the decompression group, and the decompression group had a higher skin innervation index of SP than the CCI group (0.45 ± 0.05 vs. 0.16 ± 0.03, p < 0.001). These indexes were similar in both groups for PGP 9.5 (0.32 ± 0.09 vs. 0.14 ± 0.04, p = 0.11) and CGRP (0.38 ± 0.06 vs. 0.21 ± 0.07, p = 0.09). These findings demonstrate the temporal changes in the disappearance of neuropathic pain behaviors after decompression and suggest that decompression causes different patterns of skin reinnervation for different markers of skin innervation.