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Background. One of the key distinctions between multifocal motor neuropathy (MMN) and multifocal variant of chronic inflammatory demyelinating polyradiculoneuropathy (mCIDP) lies in the presence or absence of sensory deficits. Nevertheless, existing literature suggests that MMN can also involve sensory fibers of peripheral nerves, complicating the differential diagnosis of MMN and mCIDP, which remains a relevant issue.Aim. To evaluate the profile and intensity of objective sensory deficits and autonomic dysfunction in MMN and mCIDP, as well as to identify differential diagnostic markers.Materials and methods. Out of 65 patients followed up in the study, 30 were diagnosed with MMN and 35 were diagnosed with mCIDP. A retrospective analysis of clinical and epidemiological characteristics was carried out. The evaluation encompassed clinical assessments of sensory symptoms (including on the NTSS-9 scale), assessments of the severity of autonomic dysfunction using the COMPASS-31 questionnaire, and neurophysiological multimodal sensory testing (including electroneuromyography, computer pallesthesiometry, and short-latency auditory evoked potentials).Results. Patients with mCIDP were significantly more likely to have subjective (according to the NTSS-9 and COMPASS-31 scales) and objective (according to clinical examination) sensory deficits and autonomic dysfunction (p 0.05). Electroneuromyography studies revealed significantly lower amplitudes of hand sensory nerve action potentials in the mCIDP group compared to MMN patients (p

A peripheral nerve injury results in disruption of the fiber that usually protects axons from the surrounding environment. Severed axons from the proximal nerve stump are capable of regenerating, but axons are exposed to a completely new environment. Regeneration recruits cells that produce and deposit key molecules, including growth factor proteins and fibrils in the extracellular matrix (ECM), thus changing the chemical and geometrical environment. The regenerating axons thus surf on a newly remodeled micro-landscape. Strategies to enhance and control axonal regeneration and growth after injury often involve mimicking the extrinsic cues that are found in the natural nerve environment. Indeed, nano- and micropatterned substrates have been generated as tools to guide axons along a defined path. The mechanical cues of the substrate are used as guides to orient growth or change the direction of growth in response to impediments or cell surface topography. However, exactly how axons respond to biophysical information and the dynamics of axonal movement are still poorly understood. Here we use anisotropic, groove-patterned substrate topography to direct and enhance sensory axonal growth of whole mouse dorsal root ganglia (DRG) transplanted ex vivo. Our results show significantly enhanced and directed growth of the DRG sensory fibers on the hemi-3D topographic substrates compared to a 0 nm pitch, flat control surface. By assessing the dynamics of axonal movement in time-lapse microscopy, we found that the enhancement was not due to increases in the speed of axonal growth, but to the efficiency of growth direction, ensuring axons minimize movement in undesired directions. Finally, the directionality of growth was reproduced on topographic patterns fabricated as fully 3D substrates, potentially opening new translational avenues of development incorporating these specific topographic feature sizes in implantable conduits in vivo. [ABSTRACT FROM AUTHOR]

A peripheral nerve injury results in disruption of the fiber that usually protects axons from the surrounding environment. Severed axons from the proximal nerve stump are capable of regenerating, but axons are exposed to a completely new environment. Regeneration recruits cells that produce and deposit key molecules, including growth factor proteins and fibrils in the extracellular matrix (ECM), thus changing the chemical and geometrical environment. The regenerating axons thus surf on a newly remodeled micro-landscape. Strategies to enhance and control axonal regeneration and growth after injury often involve mimicking the extrinsic cues that are found in the natural nerve environment. Indeed, nano- and micropatterned substrates have been generated as tools to guide axons along a defined path. The mechanical cues of the substrate are used as guides to orient growth or change the direction of growth in response to impediments or cell surface topography. However, exactly how axons respond to biophysical information and the dynamics of axonal movement are still poorly understood. Here we use anisotropic, groove-patterned substrate topography to direct and enhance sensory axonal growth of whole mouse dorsal root ganglia (DRG) transplanted ex vivo. Our results show significantly enhanced and directed growth of the DRG sensory fibers on the hemi-3D topographic substrates compared to a 0 nm pitch, flat control surface. By assessing the dynamics of axonal movement in time-lapse microscopy, we found that the enhancement was not due to increases in the speed of axonal growth, but to the efficiency of growth direction, ensuring axons minimize movement in undesired directions. Finally, the directionality of growth was reproduced on topographic patterns fabricated as fully 3D substrates, potentially opening new translational avenues of development incorporating these specific topographic feature sizes in implantable conduits in vivo.

Itch is the most common chief complaint in patients visiting dermatology clinics and is analogous to cough and also sneeze of the lower and upper respiratory tract, all three of which are host actions trying to clear noxious stimuli. The pathomechanisms of these symptoms are not completely determined. The itch can originate from a variety of etiologies. Itch originates following the activation of peripheral sensory nerve endings following damage or exposure to inflammatory mediators. More than one sensory nerve subtype is thought to subserve pruriceptive itch which includes both unmyelinated C-fibers and thinly myelinated Aδ nerve fibers. There are a lot of mediators capable of stimulating these afferent nerves leading to itch. Cough and itch pathways are mediated by small-diameter sensory fibers. These cough and itch sensory fibers release neuropeptides upon activation, which leads to inflammation of the nerves. The inflammation is involved in the development of chronic conditions of itch and cough. The aim of this review is to point out the role of sensory nerves in the pathogenesis of cough and itching. The common aspects of itch and cough could lead to new thoughts and perspectives in both fields. [ABSTRACT FROM AUTHOR]

Objective The interplay between neuronal innervation and other cell types underlies the physiological functions of the dura mater and contributes to pathophysiological conditions such as migraine. We characterized the extensive, but understudied, non-arterial diffuse dural innervation (DDI) of the rat and Rhesus monkey. Methods We used a comprehensive integrated multi-molecular immunofluorescence labeling strategy to extensively profile the rat DDI and to a lesser extent that of the Rhesus monkey. Results The DDI was distributed across a dense, pervasive capillary network and included free nerve endings of peptidergic CGRP-expressing C fibers that were closely intertwined with noradrenergic (NA) sympathetic fibers and thin-caliber nonpeptidergic "C/Aδ" fibers. These newly identified C/Aδ fibers were unmyelinated, like C fibers, but expressed NF200, usually indicative of Aδ fibers, and uniquely co-labeled for the CGRP co-receptor, RAMP1. Slightly-larger caliber NF200-positive fibers co-labeled for myelin basic protein (MBP) and terminated as unbranched corpuscular endings. The DDI peptidergic fibers co-labeled for the lectin IB4 and expressed presumably excitatory α1-adrenergic receptors, as well as inhibitory 5HT1D receptors and the delta opioid receptor (δOR), but rarely the mu opioid receptor (µOR). Labeling for P2X3, TRPV1, TRPA1, and parasympathetic markers was not observed in the DDI. Interpretation These results suggest potential functional interactions, wherein peptidergic DDI fibers may be activated by stress-related sympathetic activity, resulting in CGRP release that could be detected in the circulation. CGRP may also activate nonpeptidergic C/Aδ fibers that are likely mechanosensitive or polymodal, leading to activation of post-synaptic pain transmission circuits. The distribution of α1-adrenergic receptors, RAMP1, and the unique expression of the δOR on CGRP-expressing DDI fibers suggest strategies for functional modulation and application to therapy. [ABSTRACT FROM AUTHOR]

Objective: Routine electrodiagnosis (EMG-NCS) has some shortcomings in the evaluation of peripheral nervous system, auch as autonomous nervous system evaluation, in pure sensory radiculopathies and acute hyperesthetic stages of neuropathies. Quantitative sensory testings such as current perception threshold (CPT) with electrical stimulations are suggested for above mentioned pathologies. Ttest results should be compared with a normal value of similar identical population. This study is conducted to determine normal value and reproducibility of CPT in the Iranian population. Materials & Methods: Fifty normal volunteers (32 men, 18 woman) in the range of 20-40 years without exclusion criteria (such as neuro- musculoskeletal disorders, diabetes mellitus and alcoholism) were recruited with simple randomized selection and CPT test was conducted on C8 (4th finger) and L5 (1st Toe)dermatomes. To determine test’s reproducibility, 6 persons (4 men, 2 women) were examined 3 times a day, 2 day per week. Collected data were analyzed to determine mean and standard deviation. Results: Normal values of CPT test was defined as one standard deviation from mean of our CPT data. These values are in C8 dermatome 2000 Hz: 2.04± 47 250 Hz: 0.75±0.25 5 Hz: 0.76±0.3 and for L5 dermatome 2000Hz: 2.83± 0.73 250 Hz: 1.24 ± 45 5Hz: 0.76± 0.3 To determine our results reproducibility and reliability, Alpha- cronbach (existed in SPSS software) was used and %98.5 & 99% were obtained for C8 & L5 dermatomes respectively. Conclusion: Our findings are about C8 & L5 dermatomes which could be used as a normal Values for such dermatomes. Regarding to its good correlation with international results we can use international references as a normal Valueswith consideration of each clinic’s reproducibility should be assessed individually.

Cutaneous current-induced vasodilation (CIV) in response to galvanic current application is an integrative model of neurovascular interaction that relies on capsaicin-sensitive fiber activation. The upstream and downstream mechanisms related to the activation of the capsaicin-sensitive fibers involved in CIV are not elucidated. In particular, the activation of cutaneous transient receptor potential vanilloid type-1 (TRPV1) channels and/or acid-sensing ion channels (ASIC) (activators mechanisms) and the release of calcitonin gene-related peptide (CGRP) and substance P (SP) (effector mechanisms) have been tested. To assess cathodal CIV, we measured cutaneous blood flow using laser Doppler flowmetry for 20 min following cathodal current application (240 s, 100 μA) on the skin of the thigh in anesthetized healthy rats for 20 min. CIV was studied in rats treated with capsazepine and amiloride to inhibit TRPV1 and ASIC channels, respectively; CGRP8-37 and SR140333 to antagonize CGRP and neurokinin-1 (NK1) receptors, respectively; compared to their respective controls. Cathodal CIV was attenuated by capsazepine (12 ± 2% vs 54 ± 6%, P < 0.001), amiloride (19 ± 8% vs 61 ± 6%, P < 0.01), CGRP8-37 (15 ± 6% vs 61 ± 6%, P < 0.001) and SR140333 (9 ± 5% vs 54 ± 6%, P < 0.001) without changing local acidification. This is the first integrative study performed in healthy rats showing that cutaneous vasodilation in response to cathodal stimulation is initiated by activation of cutaneous TRPV1 and ASIC channels likely through local acidification. The involvement of CGRP and NK1 receptors suggests that cathodal CIV is the result of CGRP and SP released through activated capsaicin-sensitive fibers. Therefore cathodal CIV could be a valuable method to assess sensory neurovascular function in the skin, which would be particularly relevant to evaluate the presence of small nerve fiber disorders and the effectiveness of treatments. [ABSTRACT FROM AUTHOR]

Background and Aim: TLQP-21, a peptide derived from the vgf gene, has been reported to play a role in the regulation of rat gastric motility, but its influence on gastric mucosal integrity is unknown. Experimental Approach: We investigated the effects of central (0.8-8 nmol/rat) or peripheral (48-240 nmol/kg) TLQP-21 administration on ethanol- (EtOH, 50%, 1 ml/rat) induced gastric lesions in the rat. The mechanisms involved in such activity were also examined. Results: Central TLQP-21 injection dose-dependently reduced EtOH-induced gastric lesions (ED50 = 3.16 nmol), while peripheral TLQP-21 administration had no effect. The TLQP-21 gastroprotective effect against EtOH injury was accompanied by a significant increase in gastric prostaglandin E2 (PGE2) production linked to an increase in constitutive cyclooxygenase (COX) expression. The nitric oxide (NO) synthase inhibitor L-NAME (70 mg/kg, s.c.), the nonselective COX inhibitor indomethacin (10 mg/kg, orally) and capsaicin denervation removed TLQP-21 gastroprotection. Conclusions: This study shows for the first time that central TLQP-21 exerts a protective action on the gastric mucosa exposed to the noxious agent EtOH. TLQP-21 gastroprotection is mediated by constitutive-derived NO and PGE2, and requires the integrity of sensory nerve fibers. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Summary: Objective: To determine whether 5Hz and 2000Hz sinusoidal electric currents evoke different sensations and to indirectly evaluate which peripheral nerve fibers are stimulated by these different frequencies. Methods: One hundred and fifty subjects chose three among eight descriptors of sensations evoked by 5Hz and 2000Hz currents and the results were submitted to factor analysis. In 20 subjects, reaction times to 5, 250 and 2000Hz currents were determined at 1.1x ST and reaction times to 5Hz currents were also determined at 2x ST. Results: Responses were grouped in four factors: Factor 1, which loaded mainly in descriptors related to tweezers stimulation, was higher than the other factors during 2000Hz stimulation at 1.5x ST. Factor 2, which loaded mainly in descriptors related to needle stimulation, was higher than the other factors during 5Hz stimulation. Factor 1 increased and Factor 2 decreased with an increase in 5Hz intensity from 1.5 to 4x ST. Reaction times measured from the fastest responses were significantly different: 0.57s (0.16 to 1.60), 0.34s (0.12 to 0.71) and 0.22s (0.08 to 0.35) for 5, 250 and 2000Hz, respectively, and 0.22s (0.11 to 0.34) for 5Hz at 2x ST. Conclusions: Sinusoidal electrical stimulation of 5Hz and 2000Hz evoke different sensations. At juxta-threshold intensities, RT measurements suggest that 2000Hz stimulates Aβ-fibers, 250Hz Aβ- or A∂-fibers, 5Hz Aβ-, A∂- or C-fibers. The fiber type, which was initially stimulated by the lower frequencies, depended on inter-individual differences. [Copyright &y& Elsevier]

We have investigated the effect of intravaginal application of capsaicin on micturition reflex in female rats. Urinary bladder contractility was measured by transurethral pressure recording at isovolumetric and subthreshold conditions in anaesthetized rats. The intravaginal application of capsaicin (15 μg/50 μl rat) induced reproducible bladder phasic contractions, without desensitization upon repeated applications, that were blocked by intravenous atropine (1 mg/kg) or hexamethonium (5 mg/kg) and prevented by removal of paracervical ganglia or systemic capsaicin pretreatment (125 mg/kg, s.c.). The inhibition of sympathetic transmission by guanethidine (30 mg/kg, s.c.) produced significant increase of the bladder reflex contractions activated by intravaginal capsaicin. Intravenous administration of the TRPV1 antagonist, capsazepine (3 mg/kg), significantly reduced the excitatory reflex response to capsaicin. Intravaginal administration of capsaicin (15 μg/50 μl), during distension-induced reflex bladder contractions, produced a transient block of reflexes, unaffected by guanethidine pretreatment. In conclusion, the stimulation of capsaicin-sensitive sensory nerve endings in the rat cervix–vagina induced a dual excitatory or inhibitory bladder response in anaesthetized female rats depending on the degree of bladder distension. [ABSTRACT FROM AUTHOR]

Abstract: Further understanding of pathophysiology of postoperative acute pain is necessary for its better management. The methodology of current threshold (CT) determination by using sine-wave stimuli at 3 frequencies has been used to selectively and quantitatively analyze the function of the subsets of fibers (i.e., frequency of 5, 250, and 2000Hz recruits C-, Aδ-, and Aβ-fibers, respectively). This study investigated how surgical incision would affect the CTs, and then assessed the efficacy of intrathecal pharmacotherapy. The CT required to evoke a paw withdrawal response was assessed over time at stimulus frequencies of 5Hz (CT5), 250Hz (CT250), and 2000Hz (CT2000) in rats that had undergone surgical incision of the plantar skin and muscle. The CTs at all frequencies significantly decreased immediately after the incision. The decreased thresholds gradually recovered during the first week post-surgery. CT5 and CT250 (but not CT2000) remained significantly low even on day 7 post-surgery. Morphine at 5μg/10μL i.t. significantly reversed CT5 and CT250. NBQX (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid [AMPA]/kainate receptor antagonist) at 1.9 or 3.8μg/10μL i.t. significantly increased the thresholds over the pre-surgery threshold levels at all frequencies. MK-801 (N-methyl d-aspartate [NMDA] receptor antagonist) up to 13.5μg/10μL i.t. did not significantly affect CTs at any frequencies. In conclusion, a broad spectrum of sensory fibers (Aβ, Aδ, and C) is sensitized at the spinal and/or peripheral level in the postoperative acute pain state. Spinal AMPA/kainate receptors but not NMDA receptors play a significant role in this sensitization. [Copyright &y& Elsevier]

Abstract: We have used a pharmacological approach to study the mechanisms underlying the rat lung injury and the airway reactivity changes induced by inhalation of formaldehyde (FA) (1% formalin solution, 90 min once a day, 4 days). The reactivity of isolated tracheae and intrapulmonary bronchi were assessed in dose–response curves to methacholine (MCh). Local and systemic inflammatory phenomena were evaluated in terms of leukocyte countings in bronchoalveolar lavage (BAL) fluid, blood, bone marrow lavage and spleen. Whereas the tracheal reactivity to MCh did not change, a significant bronchial hyporesponsiveness (BHR) was found after FA inhalation as compared with naive rats. Also, FA exposure significantly increased the total cell numbers in BAL, in peripheral blood and in the spleen, but did not modify the counts in bone marrow. Capsaicin hindered the increase of leukocyte number recovered in BAL fluid after FA exposure. Both compound 48/80 and indomethacin were able to prevent the lung neutrophil influx after FA, but indomethacin had no effect on that of mononuclear cells. Following FA inhalation, the treatment with sodium cromoglycate (SCG), but not with the nitric oxide (NO) synthase inhibitor l-NAME, significantly reduced the total cell number in BAL. Compound 48/80, l-NAME and SCG significantly prevented BHR to MCh after FA inhalation, whereas capsaicin was inactive in this regard. On the other hand, indomethacin exacerbated BHR. These data suggest that after FA inhalation, the resulting lung leukocyte influx and BHR may involve nitric oxide, airway sensory fibers and mast cell-derived mediators. The effect of NO seemed to be largely restricted to the bronchial tonus, whereas neuropeptides appeared to be linked to the inflammatory response, therefore indicating that the mechanisms responsible for the changes of airway responsiveness caused by FA may be separate from those underlying its inflammatory lung effects. [Copyright &y& Elsevier]

Abstract: Tachykinins including substance P (SP) are well known to play a role in influencing oedema formation and leukocyte accumulation during tissue insult and inflammation. Cutaneous inflammatory models to characterize a TNFα-dependent mechanism where endogenous SP act via the NK1 receptor to promote leukocyte accumulation in the absence of oedema formation were used. We found that TNFα induced dose-dependent leukocyte accumulation at 4 h, which returned towards basal levels at 8 h in NK1 +/+ mice. This response was absent in both the NK1 +/+ mice treated with an NK1 receptor antagonist and NK1 −/− mice. At the highest dose IL-6 induced a significant accumulation in NK1 +/+ and NK1 −/− mice but IL-12 was ineffective. SP induced skin oedema but none of the cytokines did. Either co-injection of SP with low dose of TNFα (0.3 pmol/site) or SP previously injected (30 min) to TNFα evoked a significant increase in MPO activity when compared with that induced by the cytokine alone. In contrast, SP injected i.d. 3.5 h after TNFα failed to produce additive response. Control, but not capsaicin-pretreated rats (to deplete sensory nerves), exhibited a marked increase in MPO activity in response to TNFα. Histological analysis showed that TNFα caused tissue infiltrate of leukocytes in NK1 +/+ mice, whilst leukocytes accumulated at intravascular sites in NK1 −/− mice, but did not appear to emigrate, suggesting a defect in trans-endothelial migration. Interestingly, monocytes in addition to neutrophils accumulated 4 h post TNFα injection. In conclusion, the NK1 receptor plays a functional role in mediating leukocyte accumulation independently of the historically important NK1 mediated oedema formation. It seems that TNFα directly activates sensory nerve in addition to its chemoattractant activity. The NK1 receptor agonist influences the accumulation of monocytes in addition to that of PMN by 4 h, thus revealing an important influence of the NK1 receptor on TNFα mediated events in mouse skin. [Copyright &y& Elsevier]

Abstract: Objectives:: To determine the distribution of sensory fibers immunoreactive to the pain receptor TRPV1 in the human prostate. Methods:: Eight prostates were harvested from cadaver transplant donors and immediately immersion fixed. Longitudinal and transverse 20μm sections were cut on a cryostat and immunoreacted with two anti-human TPRV1 antibodies. Results:: TRPV1-immunoreactive nerve fibers were distributed throughout the prostatic urethral mucosa, verumontanum, ejaculatory ducts and periurethral prostatic acini. In the urethral mucosa, TRPV1-immunoreactive fibers penetrated the epithelial layer up to its surface. In the transitional and peripheral zones of the gland no TRPV1-immunoreactive nerve fibers were detected. Conclusions:: The existence of a rich TRPV1 sensory innervation in the human prostate may open new therapeutic perspectives for the treatment of pain in patients with chronic prostatitis (Chronic Pelvic Pain Syndrome). [Copyright &y& Elsevier]

: Background contextAn annular tear extending to the outer one-third of the annulus is thought to be one of the causes of low back pain. However, some patients have bilateral low back symptoms, even if the annular tear is localized in the lateral disc. Because nociceptive information from the lateral disc is transmitted by the dorsal root ganglion (DRG) neurons innervating the lateral disc, we investigated the distribution of the DRG neurons innervating the lateral portion of the disc.: PurposeTo clarify the distribution and pathway of the DRG neurons innervating the lateral portion of the L5–L6 disc in rats.: Study design/settingUsing the retrograde tracing method, we studied the innervation pattern of the lateral portion of the L5–L6 intervertebral disc in rats.: MethodsThe retrograde transport of Fluoro-Gold (F-G; Fluorochrome, Denver, CO) was used in 22 rats. Subjects included a nontreated group (n = 16) and a sympathectomized group (n = 6). Seven days after the application of F-G crystals to the left lateral portion of the L5–L6 disc, bilateral T12–L6 DRGs were observed by fluorescent microscopy.: ResultsIn the nontreated group, of all the F-G–labeled neurons, 93.1% were present in the left DRGs and 6.9% were in the right DRGs. The number of labeled neurons was largest in the left L2 DRGs. In the sympathectomized group, the numbers of labeled neurons in the T13, L1 and L2 DRGs were significantly lower than the numbers in the nontreated group.: ConclusionResults of this study indicate that DRG neurons innervating the lateral portion of the disc are distributed mainly in the ipsilateral side but also in the contralateral side. The DRG neurons in T13, L1 and L2 innervate the lateral portion of the L5–L6 disc through the paravertebral sympathetic trunks. [Copyright &y& Elsevier]

We have reported previously that bradykinin (BK) induces potent and reproducible concentration-dependent contractions of the pig iris sphincter (PIS) muscle in vitro through the activation of BK B2 receptors. Here we attempted to investigate additional mechanisms by which BK induces contraction of the PIS in vitro. BK-mediated contraction of the PIS relied largely on the external Ca2+ influx by a mechanism sensitive to the L-, N- and P-type of Ca2+ channel selective blockers. Likewise, BK-induced contraction of the PIS was greatly inhibited by the CGRP-(8–37), NK2 or NK3 receptor antagonists (SR 48968, SR 142801), and to a lesser extent by the NK1 antagonist (FK 888). Capsaicin desensitization of PIS or capsazepine pre-incubation also significantly reduced BK-mediated contraction in the PIS. Furthermore, KT 5720 or GF 109203X (the protein kinase A and C inhibitors, respectively) also significantly inhibited BK-mediated contraction. Taken together, these results indicate that BK-mediated contraction of the PIS seems to be mediated primarily by the release of CGRP and tachykinins from sensory nerve fibers, and relies largely on extracellular Ca2+ influx via activation of L-, N- and P-type of Ca2+ channels. Finally, these responses are mediated by activation of both protein kinase A- and C-dependent mechanisms. [Copyright &y& Elsevier]

The ability of the phospholipases A2 (PLA2s) from Crotalus durissus cascavella, Crotalus durissus collilineatus and Crotalus durissus terrificus venoms and crotapotin to increase the vascular permeability in the rat skin as well as the contribution of both mast cells and sensory C-fibers have been investigated in this study. Vascular permeability was measured as the plasma extravascular accumulation at skin sites of intravenously injected 125I-human serum albumin. Intradermal injection of crotalic PLA2s (0.05–0.5 μg/site) in the rat skin resulted in dose-dependent increase in plasma extravascular whereas crotapotin (1 μg/site) failed to affect this response. Co-injection of crotapotin (1 μg/site) did not modify the increased vascular permeability induced by the PLA2s (0.05–0.5 μg/site). Previous treatment (30 min) of the animals with cyproheptadine (2 mg/kg, i.p.) markedly reduced PLA2 (0.5 μg/site)-induced oedema. In rats treated neonatally with capsaicin to deplete neuropeptides, the plasma extravasation induced by all PLA2s (0.5 μg/site) was also significantly reduced. Similarly, the tachykinin NK1 receptor antagonist SR140333 (1 nmol/site) significantly reduced the PLA2-induced oedema. In addition, the combination of SR140333 with cyproheptadine further reduced the increased plasma extravasation by PLA2 from C. d. cascavella venom, but not by PLA2 from C. d. terrificus and C. d. collilineatus venoms. Our results suggest that increase in skin vascular permeability by crotalic PLA2s is mediated by activation of sensory C-fibers culminating in the release of substance P, as well as by activation of mast cells which in turn release amines such as histamine and serotonin. [Copyright &y& Elsevier]

Objective: To define the involvement of peripheral nerve fibers in Ross syndrome.Methods: Mechanical pain perception, tactile and thermal thresholds on hand, foot dorsum, thigh, median nerve orthodromic sensory conduction velocity (SCV) and motor conduction velocity (MCV), sural nerve antidromic SCV, peroneal nerve MCV, H-reflex, F-wave, median, tibial nerve somatosensory evoked potentials (SSEPs), perioral, hand CO2 laser late (LEPs) and ultralate evoked potentials, sympathetic skin response (SSRs), cardiovascular, Minor sweat, silastic imprint, histamine, photopletysmographic and pupil pilocarpine tests, cutaneous innervation immunohistochemical techniques were studied in 3 patients with Ross syndrome.Results: Quantitative sensory testing showed altered results in patients 1 and 2, and patient 3 had a slight impairment of mechanical pain perception. Nerve conduction, except for a median nerve distal reduction of sensory conduction in patient 1, F-wave and SSEP findings were normal; H-reflex was absent at rest in all patients. Hand LEPs were absent in patient 2, ultralate potentials were absent in patients 1 and 2. Skin biopsy showed a disease duration related reduction of unmyelinated and myelinated sensory fibers and a lack of unmyelinated autonomic fibers in all patients.Conclusions: Our data suggest that Ross syndrome is a degenerative disorder involving progressive sudomotor fibers, and then epidermal sensory unmyelinated and myelinated fibers. [Copyright &y& Elsevier]

We compared the distribution of substance P (SP) and calcitonin gene-related peptide (CGRP) fibers of the superficial muscle layer (trapezius muscle), median muscle layer (rhomboideus muscle), and deep muscle layer (longissimus and spinalis muscles) of the dorsum of the rat. SP- and CGRP-immunoreactive fibers were seen along the walls of various types of blood vessels and within nerve bundles in skeletal muscles of all layers. Coexistence of SP and CGRP was evident in nerve fibers along the blood vessel walls. The total number of CGRP varicosities per millimeter square of muscle surface area was evaluated quantitatively, and CGRP varicosities were found to be significantly more numerous in the superficial muscle layer than in the deeper ones. After capsaicin treatment, most of the SP and CGRP fibers along the blood vessel walls were eliminated. These results suggest that sensory nerve fibers containing SP and CGRP are distributed more abundantly in the superficial muscle layer than in the deeper ones and that they might be involved in the regulation of local blood flow. The finding of SP- and CGRP-immunoreactive nerve fibers along the blood vessel walls connecting the trapezius muscle and the hypodermis raises the possibility that sensory stimuli to the skin affect the local blood flow of superficial muscle through collaterals of cutaneous fibers. [Copyright &y& Elsevier]

We evaluated the potency of isoproterenol, carbachol, pilocarpine and calcitonin gene-related peptide (CGRP) in the rat right atria at 30, 60 and 90 days after neonatal capsaicin treatment. Neonatal rats were pretreated on the second day of life with capsaicin (50 mg/kg). The capsaicin pretreatment caused a five-fold rightward shift at the pEC50 level on the concentration–response curves to isoproterenol in 30-day-old rats. Propranolol (10 mg/kg, given 15 min prior to capsaicin treatment) prevented this subsensitivity. No changes in the potency of isoproterenol were observed at 60 and 90 days after capsaicin pretreatment. The potency and maximal responses of CGRP in the right atria in 30-day-old rats were significantly higher than in 60- and 90-day-old rats; however, no differences were found between control and capsaicin groups. The potency and maximal responses to carbachol and pilocarpine were not changed in all groups. The neonatal capsaicin treatment reduced by about 74% the CGRP content in the heart in all groups. In summary, capsaicin treatment in newborn rats produces a desensitization of chronotropic response mediated by β-adrenoceptors in isolated right atria from 30-day-old rats possibly due to a massive release of catecholamines. [Copyright &y& Elsevier]

Kinins are mediators of pain and inflammation and evidence suggests that the inducible kinin B1 receptor (B1R) is involved in neuropathic pain (NP). This study investigates whether B1R and TRPV1 are colocalized on nociceptors and/or astrocytes to enable regulatory interaction either directly or through the cytokine pathway (IL-1β, TNF-α) in NP. Sprague Dawley rats were subjected to unilateral partial sciatic nerve ligation (PSNL) and treated from 14 to 21 days post-PSNL with antagonists of B1R (SSR240612, 10 mg·kg−1, i.p.) or TRPV1 (SB366791, 1 mg·kg−1, i.p.). The impact of these treatments was assessed on nociceptive behavior and mRNA expression of B1R, TRPV1, TNF-α, and IL-1β. Localization on primary sensory fibers, astrocytes, and microglia was determined by immunofluorescence in the lumbar spinal cord and dorsal root ganglion (DRG). Both antagonists suppressed PSNL-induced thermal hyperalgesia, but only SB366791 blunted mechanical and cold allodynia. SSR240612 reversed PSNL-induced enhanced protein and mRNA expression of B1R and TRPV1 mRNA levels in spinal cord while SB366791 further increased B1R mRNA/protein expression. B1R and TRPV1 were found in non-peptide sensory fibers and astrocytes, and colocalized in the spinal dorsal horn and DRG, notably with IL-1β on astrocytes. IL-1β mRNA further increased under B1R or TRPV1 antagonism. Data suggest that B1R and TRPV1 contribute to thermal hyperalgesia and play a distinctive role in allodynia associated with NP. Close interaction and reciprocal regulatory mechanism are suggested between B1R and TRPV1 on astrocytes and nociceptors in NP. [ABSTRACT FROM AUTHOR]