Peripheral nerve lesion-induced uptake and transport of choleragenoid by capsaicin-sensitive c-fibre spinal ganglion neurons.
ABSTRACT In the present experiments the effect of systemic capsaicin treatment on the retrograde labelling of sensory ganglion cells was studied following the injection of choleratoxin B subunit-horseradish peroxidase conjugate (CTX-HRP) into intact and chronically transected peripheral nerves. In the control rats CTX-HRP injected into intact sciatic nerves labelled medium and large neurons with a mean cross-sectional area of 1,041 +/- 39 gm2. However, after injection of the conjugate into chronically transected sciatic nerves of the control rats, many small cells were also labelled, shifting the mean cross-sectional area of the labelled cells to 632 +/- 118 microm2. Capsaicin pretreatment per se induced a moderate but significant decrease in the mean cross-sectional area of the labelled neurons (879 +/- 79 microm2). More importantly, systemic pretreatment with capsaicin prevented the peripheral nerve lesion-induced labelling of small cells. Thus, the mean cross-sectional areas of labelled neurons relating to the intact and transected sciatic nerves, respectively, did not differ significantly. These findings provide direct evidence for a phenotypic switch of capsaicin-sensitive nociceptive neurons after peripheral nerve injury, and suggest that lesion-induced morphological changes in the spinal cord may be related to specific alterations in the chemistry of C-fibre afferent neurons rather than to a sprouting response of A-fibre afferents.
- SourceAvailable from: Julien Pelletier[show abstract] [hide abstract]
ABSTRACT: Most studies of chronic nerve compression focus on large nerve function in painful conditions, and only few studies have assessed potential changes in the function of small nerve fibers during chronic nerve compression and recovery from compression. Cutaneous pressure-induced vasodilation is a neurovascular phenomenon that relies on small neuropeptidergic fibers controlling the cutaneous microvasculature. We aimed to characterize potential changes in function of these small fibers and/or in cutaneous microvascular function following short-term (1-month) and long-term (6-month) nerve compression and after release of compression (ie, potential recovery of function). A compressive tube was left on one sciatic nerve for 1 or 6 months and then removed for 1-month recovery in Wistar rats. Cutaneous vasodilator responses were measured by laser Doppler flowmetry in hind limb skin innervated by the injured nerve to assess neurovascular function. Nociceptive thermal and low mechanical thresholds were evaluated to assess small and large nerve fiber functions, respectively. Pressure-induced vasodilation was impaired following nerve compression and restored following nerve release; both impairment and restoration were strongly related to duration of compression. Small and large nerve fiber functions were less closely related to duration of compression. Our data therefore suggest that cutaneous pressure-induced vasodilation provides a non-invasive and mechanistic test of neurovascular function that gives direct information regarding extent and severity of damage during chronic nerve compression and recovery, and may ultimately provide a clinically useful tool in the evaluation of nerve injury such as carpal tunnel syndrome.Pain 11/2011; 153(1):149-57. · 5.64 Impact Factor
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ABSTRACT: To investigate possible differential effects of the coadministration of conjugated equine estrogen (CEE) and a placebo (CEE + PL), CEE and medroxyprogesterone acetate (CEE + MPA), or CEE and micronized P (CEE + MP) on aspects of cognitive functioning in naturally postmenopausal women. Double-blind, randomized, controlled trial. Gynecologic screening occurred at a university hospital, and neuropsychological testing took place in a university laboratory. Twenty-four naturally menopausal women with an intact uterus who had never used hormone therapy were recruited by means of newspaper advertisements. All completed the study. A battery of mood and neuropsychological tests was administered. Women were randomly assigned to receive CEE + PL (n = 7), CEE + MPA (n = 9), or CEE + MP (n = 8). The tests were readministered 12 weeks later. Standardized tests of mood, verbal memory, working memory, spatial abilities, and visual-spatial sequencing, and assays of serum sex hormone levels. Mood improved after treatment in all groups. No changes in scores occurred over time in any cognitive test in the group that received CEE + PL. Only the CEE + MP group had a significant decrease in their delayed verbal memory scores from baseline to after treatment. The CEE + MP-treated women performed significantly better on a test of working memory than women in the other two groups. Coadministration of CEE with MPA or MP caused differential effects on aspects of memory in postmenopausal women. These findings need to be replicated with a larger sample size before their potential clinical implications can be determined.Fertility and sterility 06/2011; 96(2):399-403. · 3.97 Impact Factor
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ABSTRACT: Recent studies have demonstrated significant changes in the neuronal ganglioside status associated with altered functional states of nociceptive primary sensory neurons. In the present study, therefore, the effects of the inhibition of glucosylceramide synthase, the key enzyme of ganglioside synthesis, were studied on chemically defined populations and on the activation of TRPV1 of cultured adult rat sensory ganglion neurons. In control cultures, capsaicin resulted in the activation of TRPV1 in 29.7+/-2.5% of the neurons, as assessed with the cobalt uptake assay. Pretreatment of the cultures for 4days with an inhibitor of glucosylceramide synthase, d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (d-PDMP), significantly decreased the proportion of capsaicin-activated neurons to 11.6+/-1.2%. Immunohistochemistry demonstrated that, in control cultures, 37.5+/-1.4% of the neurons displayed TRPV1 immunoreactivity, whereas in d-PDMP-treated cultures the proportion of TRPV1-immunoreactive neurons was diminished to 18.2+/-2.1%. Further experiments disclosed that these effects of d-PDMP were reversible. The capsaicin-, but not the high potassium-induced release of CGRP, was also significantly reduced after d-PDMP treatment, as measured with ELISA. The proportions of IB4- and CGRP-positive neurons were not significantly affected by d-PDMP. The present observations demonstrate that inhibition of neuronal ganglioside synthesis profoundly modulates the expression of the TRPV1 receptor, apparently leaving other markers of nociceptive neurons, such as CGRP and IB4, unaffected. The findings indicate that as yet unidentified ganglioside(s) synthesized by the glucosylceramide synthase pathway may be essential for nociception through mechanisms which may implicate membrane lipid raft function and/or altered nerve growth factor signaling, which are essential for the TRPV1 receptor function.Pain 07/2010; 150(1):103-12. · 5.64 Impact Factor