Influence of opioids on substance P release evoked by antidromic stimulation of primary afferent fibers in the hind instep of rats

Substance P appears to be involved in the transmission of pain signals from the periphery to the spinal cord and brain stem. Substance P containing neurons are responsible for the neurogenic vasodilation identical to that obtained by substance P release evoked by antidromic stimulation of these fibres. Both endogenous opioids and somatostatin inhibit the release of substance P from central and peripheral endings. Present pharmacological investigations conclude that morphine and somatostatin are as effective as ergotamine in reducing the pain of CH. All three drugs are significantly more active than placebo. Somatostatin and opiates could act by inhibiting the release of substance P. La Substance P (SP) représente le probable transmitteur des sensations douloureuses de la périphérie à la moelle épinière et au tronc encéphalique. Les neurones contenants la SP semblent être aussi responsables de la vasodilatation neurogenique identique à celle qui peut être obtenue par le “release” de SP, induit par la stimolation antidromique de ces fibres. Soit ces opiaces endogènes que la somatostatine (SR1F) inhibent le “release” de SP par les terminaisons nerveuses céntrales et périphériques. Notre étude clinique parvient à la conclusion que la morphine et le SRIF ont une efficacité semblabe à celle de l'ergotamine en rediure la douleur pendant l'attaque de céphalée “en chapelet”, et que tous les troi medicaments sont significativement actifs plus que le placebo. Le SRIF et les opiacés pourraient agir en inhibant le “release” de SP par les terminaissons neuronales céntrales et périphériques. La sostanza P viene indicata come il probabile trasmettitore delle sensazioni dolorifiche dalla periferia al midollo spinale ed al tronco encefalico. I neuroni contenenti SP sembrano inoltre essere responsabili della vasodilatazione neurogenica identica a quella ottenibile dal “release” di SP indotto dalla stimoalzione antidromica di queste fibre. Sia gli oppiacei endogeni che la Somatostatina inibiscono il “release” di sostanza P dai terminali nervosi centrali e periferici. Dalla presente ricerca emerge che la morfina ed il SRIF hanno una efficacia simile a quella dell'ergotamina nel ridurre il dolore nell'attacco di CH, e che tutti e tre i farmaci sono significativamente più attivi rispetto al placebo. SRIF ed oppiacei potrebbero agire inibendo il release di SP dalle terminazioni nervose sia a livello centrale che periferico.

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Functional specialization of central projections from identified primary afferent fibers

Journal of Neurophysiology ◽

10.1152/jn.1988.60.5.1597 ◽

1988 ◽

Vol 60 (5) ◽

pp. 1597-1614 ◽

Cited By ~ 43

Author(s):

H. R. Koerber ◽

L. M. Mendell

Keyword(s):

Test Stimulus ◽

Conditioning Stimulus ◽

Hair Follicles ◽

Single Fiber ◽

High Frequency Stimulation ◽

High Threshold ◽

Primary Afferent ◽

Afferent Fibers ◽

Primary Afferent Fibers ◽

Stimulation Of

1. Somata of primary afferent fibers were impaled in the L7 or S1 dorsal root ganglion in cats anesthetized with alpha-chloralose. Individual cells (n = 182) were characterized according to receptive field (RF) and by the peripheral mechanoreceptor they innervated. They were then stimulated intracellularly while recording the evoked cord dorsum potentials (CDPs) simultaneously at four sites. CDPs were recorded in response to single fiber stimulation while varying both the frequency and the numbers of action potentials (APs) evoked per trial. Stimulus parameters included: 1) single APs evoked at both high (18 Hz) and low (0.67 Hz) frequencies, 2) pairs of APs (50-ms ISI) delivered at 0.67 Hz, and 3) trains of four APs (20-ms ISI) also delivered at 0.67 Hz. The properties of the CDPs and their relationship to receptor type innervated by the fiber were determined. 2. CDPs evoked by 18-Hz stimulation consisted of an axon fiber spike followed at a short latency [600 +/- 9.9 (SEM) microseconds] by the onset of a monophasic negative wave. A-beta-afferent fibers innervating slowly adapting type 1 and 2 receptors (SA1 and SA2) evoked the largest amplitude CDPs followed by field and hair follicle afferents while A-delta-fibers rarely produced measurable CDPs at this frequency of stimulation. 3. The magnitude of the CDP varied at the four recording sites with clear evidence in individual experiments that the projections of individual fibers are somatotopically organized. 4. CDPs evoked by 0.67-Hz stimulation had the same onset latency but were larger in amplitude and had longer time-to-peak and durations than those elicited by high frequency stimulation. Under these conditions A-beta-fibers innervating hair follicles produced the largest CDPs followed by field receptors and SA1s and SA2s. A-beta- and A-delta-fibers innervating high threshold mechanoreceptors (HTMRs) and A-delta-fibers innervating down hair follicles (D-hairs) produced CDPs of amplitude and duration similar to those evoked by slower A-beta-fibers. 5. The response to a test stimulus delivered 50 ms after a conditioning stimulus to the same single fiber was always depressed in the case of A-beta-fibers supplying rapidly adapting receptors. The conditioning stimulus exerted relatively little effect on the response to the test stimulus for A-beta- fibers innervating slowly adapting receptors. The test response to stimulation of A-beta- and A-delta- fibers innervating HTMRs was consistently facilitated while stimulation of A-delta- D-hairs evoked either marked facilitation or slight depression.(ABSTRACT TRUNCATED AT 400 WORDS)

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