Effects of Substance P on Nociceptive and Non-Nociceptive Trigeminal Brain Stem Neurons (original) (raw)
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Electrical stimulation of the brain, particularly in the periventricular grey areas, caused long-lasting increases in behavioural escape thresholds to heating and mechanical stimuli applied to the facial region of the rat. The brain stimulation selectively suppressed responses to noxious stimuli. Responses to non-noxious stimuli, evoked by low threshold brush, were unaffected. The same animals that were studied in the behavioural tests were then anaesthetized with urethane and the inhibitory effect of the same brain stimulation was studied in single neurones recorded in the caudal trigeminal nucleus. A clear correlation (r S = 0.63) emerged between degree of behavioural antinociception and the amount of inhibition seen in nociceptive neurones. In addition the mean duration of the inhibition (6 min) was similar to the mean duration of the antinociceptive effect (7.3 min). Other classes of non-nociceptive neurones were unaffected by the stimulation. The neurones were also studied using iontophoretically applied monoamine candidates for the inhibitory neurotransmitter, noradrenaline (NA) and 5-hydroxytryptamine (5-HT). The profile of the effects of NA most closely fitted that of the inhibitory neurotransmitter. This profile was expressed in terms of depression and excitation of different classes of neurones, and by the duration of effects. The depressant effects could be antagonized by iontophoretic idazoxan. In addition clonidine induced long-lasting depression of firing. 5-HT was more likely than NA to excite nociceptive neurones and to depress non-nociceptive neurones. Only NA consistently elevated thermal response thresholds in a similar manner to that produced by brain stimulation. These results provide some support for the hypothesis that selective descending inhibition of nociceptive responses in neurones of the rat caudal trigeminal nucleus is mediated by NA, possibly by an action at a2-adrenoceptors.
Brain Research, 1995
Electrical stimulation of the brain, particularly in the periventricular grey areas, caused long-lasting increases in behavioural escape thresholds to heating and mechanical stimuli applied to the facial region of the rat. The brain stimulation selectively suppressed responses to noxious stimuli. Responses to non-noxious stimuli, evoked by low threshold brush, were unaffected. The same animals that were studied in the behavioural tests were then anaesthetized with urethane and the inhibitory effect of the same brain stimulation was studied in single neurones recorded in the caudal trigeminal nucleus. A clear correlation (rs = 0.63) emerged between degree of behavioural antinociception and the amount of inhibition seen in nociceptive neurones. In addition the mean duration of the inhibition (6 min) was similar to the mean duration of the antinociceptive effect (7.3 min). Other classes of non-nociceptive neurones were unaffected by the stimulation. The neurones were also studied using iontophoretically applied monoamine candidates for the inhibitory neurotransmitter, noradrenaline (NA) and 5-hydroxytryptamine (5-HT). The profile of the effects of NA most closely fitted that of the inhibitory neurotransmitter. This profile was expressed in terms of depression and excitation of different classes of neurones, and by the duration of effects. The depressant effects could be antagonized by iontophoretic idazoxan. In addition clonidine induced long-lasting depression of firing. 5-HT was more likely than NA to excite nociceptive neurones and to depress non-nociceptive neurones. Only NA consistently elevated thermal response thresholds in a similar manner to that produced by brain stimulation. These results provide some support for the hypothesis that selective descending inhibition of nociceptive responses in neurones of the rat caudal trigeminal nucleus is mediated by NA, possibly by an action at α2-adrenoceptors.
Brain Research, 1988
Intrathecal (i.t.) injection of substance P (SP), capsaicin, kainic acid, picrotoxin, strychnine, morphine, and L-glutamic acid in rats induced rhythmic scratching movements with the hindlimbs, biting, and, with some of these compounds, vocalization and myoclonic twitches. Although biting was directed to the dermatome corresponding to the injection site, scratching was aimed at anterior dermatomes. Presumably painful chemical stimulation produced by cutaneous and subcutaneous application of capsaicin or acetic acid never elicited scratching. Vocalization was never elicited by SP. When vocalization occurred following i.t. picrotoxin and morphine, it was correlated with myoclonic twitches rather than with scratching and/or biting, These findings indicate that scratching (a) is not pain-related and, (b) when elicited by the i.t. administration of the compounds listed above, does not result from activation of nociceptive primary afferent synapses. 0006-8993/88/$03.50
Pain, 2002
Although pains arising from the craniofacial complex can be severe and debilitating, relatively little is known about the peripheral and central mechanisms that generate and maintain orofacial pain. To better understand the neurons in the trigeminal complex and spinal cord that are activated following nociceptive stimuli to the orofacial complex, we examined substance P (SP) induced internalization of substance P receptors (SPR) in neurons following dental extraction in the rat. Unilateral gingival reflection or surgical extraction of a rat maxillary incisor or molar was performed and tissues harvested at various time points post-extraction. Immunohistochemical analysis of brainstem and cervical spinal cord sections was performed using an anti-SPR antibody and confocal imaging. Both the number and location of neurons showing SPR internalization was dependent on the location and extent of tissue injury. Whereas extraction of the incisor induced internalization of SPR in neurons bilaterally in nucleus caudalis and the spinal cord, extraction of the molar induced strictly unilateral internalization of SPR-expressing neurons in the same brain structures. Minor tissue injury (retraction of the gingiva) activated SPR neurons located in lamina I whereas more extensive and severe tissue injury (incisor or molar extraction) induced extensive SPR internalization in neurons located in both laminae I and III-V. The rostrocaudal extent of the SPR internalization was also correlated with the extent of tissue injury. Thus, following relatively minor tissue injury (gingival reflection) neurons showing SPR internalization were confined to the nucleus caudalis while procedures which cause greater tissue injury (incisor or molar extraction), neurons showing SPR internalization extended from the interpolaris/caudalis transition zone through the C7 spinal level. Defining the population of neurons activated in orofacial pain and whether analgesics modify the activation of these neurons should provide insight into the mechanisms that generate and maintain acute and chronic orofacial pain.
British Journal of Pharmacology, 2003
1 Opioid agonists have been used for many years to treat all forms of headache, including migraine. We sought to characterize opioid receptors involved in craniovascular nociceptive pathways by in vivo microiontophoresis of m-receptor agonists and antagonists onto neurons in the trigeminocervical complex of the cat. 2 Cats were anaesthetized with a-chloralose 60 mg kg 71 , i.p. and 20 mg kg 71 , i.v. supplements after induction and surgical preparation using halothane. Units were identi®ed in the trigeminocervical complex responding to supramaximal electrical stimulation of the superior sagittal sinus, and extracellular recordings of activity made.
Properties of nociceptive and non-nociceptive neurons in trigeminal subnucleus oralis of the rat
Brain Research, 1990
Recent studies have provided evidence suggesting the involvement of rostral components of the V brainstem complex such as trigeminal (V) subnucleus oralis in orofacial pain mechanisms. Since there has been no detailed investigation of the possible existence of nociceptive oralis neurons in the rat to substantiate this recent evidence, the present study was initiated to determine if neurons responsive to noxious orofacial stimuli were present in subnucleus oralis and to characterize their functional properties. In anesthetized rats, recordings were made of the extracellular activity of single neurons functionally characterized as low-threshold mechanoreceptive (LTM), wide dynamic range (WDR) or nociceptive-specific (NS) neurons. The 342 LTM neurons responded only to light mechanical stimulation of orofacial tissues. The mechanoreceptive field of the LTM neurons included the intraoral region in 28% and was localized to the adjacent perioral area in 65%. For 95% the field was localized within one V division. Responses evoked in LTM neurons by electrical stimulation of the orofacial mechanoreceptive field revealed A fiber afferent inputs but no activity that could be attributed to C fiber afferent inputs. The 72 nociceptive neurons included 52 WDR neurons which responded to light (e.g. tactile) as well as noxious (e.g. heavy pressure; pinch) mechanical stimulation of perioral cutaneous and intraoral structures, and 20 NS neurons which responded exclusively to noxious mechanical stimuli. They also differed from the LTM neurons in that 36% of the WDR and 20% of the NS neurons had a mechanoreceptive field involving more than one V division. However, in accordance with our findings for the LTM neurons, the majority of WDR and NS neurons had a mechanoreceptive field involving the intraoral and perioral representations of the mandibular and/or maxillary divisions; those neurons having a mandibular field which especially included intraoral structures predominated in the dorsomedial zone of subnucleus oralis whereas those with a perioral mechanoreceptive field which particularly involved the maxillary division were concentrated in the ventrolateral zone of oralis. In contrast to the LTM neurons, 57% of the WDR and 67% of the NS neurons showed evidence of electrically evoked C fiber as well as A fiber afferent inputs from their mechanoreceptive field. We also noted suppression of the electrically evoked responses by heating of the tail or pinching of the paw. This effect was considered to be a reflection of diffuse noxious inhibitory controls, and was seen in NS as well as WDR neurons; most, but not all, of these neurons received A fiber as well as C fiber orofacial afferent inputs. These findings provide support for recent evidence suggesting that V subnucleus oralis is an important element in orofacial pain processing, and further indicate that oralis may be involved particularly in intraoral and perioral nociceptive mechanisms.
Brain Research, 1984
The effects of iontophoretically applied substance P (SP), (o-Pro2,o-TrpT,9)-SP and (D-Pro 4, D-Trp 7,9, I°)-SP were studied on neurons identified by their histological location in the nucleus tractus solitarius (NTS), their response to vagal or carotid sinus nerve stimulation and eventually their functional correlation with the central respiratory drive. Potent and consistent excitatory effects of SP were found supporting its role as a putative excitatory transmitter in the NTS. The effects of SP and L-glutamate (Glu) were differentiated by the relative insensitivity of SP-induced excitations to levorphanol and Met-enkephalin. 0006-8993/84/$03.00
1988
Intrathecal (i.t.) injection of substance P (SP), capsaicin, kainic acid, picrotoxin, strychnine, morphine, and L-glutamic acid in rats induced rhythmic scratching movements with the hindlimbs, biting, and, with some of these compounds, vocalization and myoclonic twitches. Although biting was directed to the dermatome corresponding to the injection site, scratching was aimed at anterior dermatomes. Presumably painful chemical stimulation produced by cutaneous and subcutaneous application of capsaicin or acetic acid never elicited scratching. Vocalization was never elicited by SP. When vocalization occurred following i.t. picrotoxin and morphine, it was correlated with myoclonic twitches rather than with scratching and/or biting, These findings indicate that scratching (a) is not pain-related and, (b) when elicited by the i.t. administration of the compounds listed above, does not result from activation of nociceptive primary afferent synapses. 0006-8993/88/$03.50
Pain, 1990
An electrophysiological study was carried out in anesthetized rats to characterize the properties of single neurons in trigeminal (V) subnucleus caudalis. Each neuron was functionally classified ,n terms of its cutaneous mechanoreceptive field properties as low-threshold mecbanoreceptive (LTM), wide dynamic range (WDR) ~r nociceptive-specific (NS), and its responsiveness was also tested to electrical stimulation of hypogiossal (XII) nerve muscle afferents. Some neurons were also tested with noxious stimulation of the tail or forepaw for the presence of diffuse noxious inhibitory cor~trols ('DNIC) of evoked responses. A mechanoreceptive field localized to the ipsilateral orofacial region was a feature of all the neurons which were located in laminae I-VI; the LTM neurons predom;nated in laaunae Ill/IV whereas the nociceptive (WDR, NS) were located in the superficial and especially deeper laminae of caudalis. The majority of the WDR and NS neurons were also activated by noxious heating as well as by noxious mechanical and electrical stimulation of their orofacial mechanorecepti~e field, and in contrast to our previous studies i~a cats, most of these caudalis nociceptive neurons received C fiber as well as A fiber cutaneous afferent inputs. In contrast to the LTM neurons, but consistent with our previous data in cats, many of the nociceptive neurons also received convergent excitatory inputs from XII muscle afferent ~, md the stimulus-response functions of the WDR neurons indicated that they were capable of coding the intensity of A and C fiber cr~,niofacial muscle afferent inputs as well as those from cutaneous afferents. The study has also documented for the first time that muscle afferent-evoked responses as well as those evoked by cutaneous afferent inputs to nociceptive neurons are subject to DNIC. These findings indicate that subnucleus caudalis plays an important role in the transmission of superficial and deep nociceptive information from the craniofacial region of the rat, and also reveal that responses of the nociceptive neurons evoked by deep as well as superficial afferent inputs can be powerfully modulated by other nociceptive influences originating from widespread parts of the body.