5-HT3 receptor binding sites are on capsaicin-sensitive fibres in the rat spinal cord

Hamon, Michel; Gallissot, M.C.; Menard, Fanny; Gozlan, H.; Bourgoin, S.; Vergé, Daniel

doi:10.1016/0014-2999(89)90472-x

Cited by 176 publications

(67 citation statements)

References 32 publications

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“…The number of 5-HT 3 receptors in the dorsal horn can be greatly reduced by neonatal capsaicin treatment or dorsal rhizotomy, 55,56 which suggests that these receptors are expressed predominantly on peripheral nerve fibers and terminals, but that those remaining may represent 5-HT 3 receptors on inhibitory interneurons in the spinal cord. 57 Given the predominantly pronociceptive effect of 5-HT acting at 5-HT 3 receptors, however, and the clinical analgesic potential of the selective 5-HT 3 receptor antagonist ondansetron, 58 these presumptive GABA-dependent inhibitory effects may be masked by upregulated descending serotonergic facilitatory effects in the pathophysiological setting.…”

Section: -Ht Function In Different Pain Statesmentioning

confidence: 99%

Preclinical and Early Clinical Investigations Related to Monoaminergic Pain Modulation

2009

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Summary:The balance between descending controls, both excitatory and inhibitory, can be altered in various pain states. There is good evidence for a prominent ␣ 2 -adrenoceptor-mediated inhibitory system and 5-HT 3 (and likely also 5-HT 2 ) serotonin receptor-mediated excitatory controls originating from brainstem and midbrain areas. The ability of cortical controls to influence spinal function allows for top-down processing through these monoamines. The links between pain and the comorbidities of sleep problems, anxiety, and depression may be due to the dual roles of noradrenaline and of 5-HT in these functions and also in pain. These controls appear, in the cases of peripheral neuropathy, spinal injury, and cancer-induced bone pain to be driven by altered peripheral and spinal neuronal processes; in opioid-induced hyperalgesia, however, the same changes occur without any pathophysiological peripheral process. Thus, in generalized pain states in which fatigue, mood changes, and diffuse pain occur, such as fibromyalgia and irritable bowel syndrome, one could suggest an abnormal engagement of descending facilitations with or without reduced inhibitions but with central origins. This would be an endogenous central malfunction of top-down processing, with the altered monoamine systems underlying the observed symptoms. A number of analgesic drugs can either interact with or have their actions modulated by these descending systems, reinforcing their importance in the establishment of pain but also in its control. Key Words: 5-HT receptors, 5-HT, serotonin, noradrenaline, RVM, rostral ventromedial medulla, opioidinduced hyperalgesia, neuropathy, fibromyalgia. PAIN, COMORBIDITIES, AND MONOAMINESPain and mood share certain neurological pathways in the CNS and have overlapping neurochemical bases, in particular their modulation by monoamine systems. This provides the substrate through which pain can influence mood, giving rise to comorbidities or secondary symptoms such as anxiety and depression, 1,2 and by the same continuum allows mood to exacerbate pain; indeed, patients with depression often present with symptoms that include medically unexplained pain, with the mean prevalence of such occurrence cited as 65%.1,3 Emotional facets of nociception play a significant role in the pain experience, with fear largely driving adaptive behaviors that enable avoidance of actual or impending harm. This therefore subserves the key function of pain, to protect the integrity and survival of an organism. Moreover, the role of emotions and state of mind in pain partly underlie the variable relationship between the intensity of damaging stimuli and perceived pain, such that at any given time and for any given nociceptive stimulus, painful response can be influenced by emotional state (the psychological context in which the stimulus is received), emotional trait (the psychological characteristics of the recipient), and cognitive set (attention and vigilance, for example).Depression is associated with abnormalities in the monoaminergic ...

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Section: -Ht Function In Different Pain Statesmentioning

confidence: 99%

Preclinical and Early Clinical Investigations Related to Monoaminergic Pain Modulation

2009

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“…2 IT opioid-induced itching may be related to the cephalad spread of the drug in the cerebrospinal fluid and its action on both µ receptors (in the medulla), 5,9,10 and central serotonin type 3 receptors (in the spinal cord and medulla). 11,12 Therefore, opioids that do not cause peripheral histamine release can still cause itching. 2,3 Opioids administered (both systemically and regionally) reach central neural centres.…”

Section: R Re Es Su Ul Lt Ts Smentioning

confidence: 99%

L’administration prophylactique d’ondansétron ne réduit pas l’incidence de prurit induit par le sufentanil intrathécal

Waxler

Mondragon

Patel

et al. 2004

Can J Anesth/J Can Anesth

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P Pu ur rp po os se e: : Postoperative itching after intrathecal (IT) narcotics may be a difficult and important problem for both the anesthesiologist and the patient in the postanesthetic care unit. Since some studies have reported success in preventing itching with ondansetron, we designed a prospective, randomized, double-blinded, and controlled study to test whether prophylactic iv ondansetron effectively reduces the incidence of IT sufentanil-induced pruritus.M Me et th ho od ds s: : Thirty-four patients (ASA I-III, age 18-74 yr) underwent ambulatory surgery after spinal anesthesia with IT lidocaine (15-100 mg) and IT sufentanil (10 µg). The patients were randomized into two groups to receive iv either 4 mL saline (n = 13) or 8 mg ondansetron (n = 21) before the IT injection. The incidence of pruritus and other variables was recorded. Pruritus scores were obtained with a verbal analogue score with 0 meaning none and 10 the worst itching that the patient could imagine. Statistical difference was assumed if P < 0.05. R Re es su ul lt ts s: : Ondansetron did not reduce the incidence of pruritus (77 vs 81%) compared to placebo (P = 1.000). The pruritus scores (4.4 vs 3.6) of the two groups were not significantly different (P = 0.670).C Co on nc cl lu us si io on ns s: : There are contradictory findings in the literature regarding the effectiveness of ondansetron in preventing narcoticinduced itching. Although some studies have indicated that ondansetron could prevent this side effect of IT narcotics, a recent report suggested that ondansetron is not effective in preventing narcotic-induced itching (sufentanil-morphine) after a Cesarean section. In the present study we obtained similar, negative results. Objectif : Le prurit postopératoire induit par l'administration intrathé-cale (IT) de narcotiques est un problème important pour l'anesthésio-logiste et le patient en salle de réveil. Certaines études ont montré que l'ondansétron prévenait le prurit. Notre étude prospective, randomisée, contrôlée et à double insu voulait vérifier si l'administration iv préventive d'ondansétron réduit effectivement l'incidence de prurit induit par le sufentanil IT. Méthode : Trente-quatre patients (ASA I-III, de 18 à 74 ans) ont subi une intervention chirurgicale ambulatoire sous rachianesthésie avec de la lidocaïne IT (15-100 mg) et du sufentanil IT (10 µg). Les patients, randomisée en deux groupes, ont reçu soit 4 mL de solution saline iv (n = 13), soit 8 mg d'ondansétron (n = 21) avant l'injection IT. L'incidence de prurit et d'autres variables a été notée. Les scores de

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“…This however opposes the attenuation of aerent-evoked neurotransmission observed by Khasabov et al (1999) in similarly aged animals when CPBG was applied at much higher concentrations (10 ± 50 mM). Since the vast majority of 5-HT 3 receptors present in the spinal cord dorsal horn are found on primary aerent terminals (Hamon et al, 1989;Kidd et al, 1993;Laporte et al, 1995) where they can mediate a primary aerent depolarization (Khasabov et al, 1999), synaptic depression via presynaptic inhibitory mechanisms is expected. Even though 5-HT 3 receptors are also present on some dorsal horn neurons including GABAergic (Morales et al, 1998) and enkephalinergic interneurons (Tsuchiya et al, 1999), we found no evidence to suggest that CPBG mediated direct excitatory actions on the DDH neurons.…”

Section: Synaptic Facilitationmentioning

confidence: 99%

Pharmacological characterization of serotonin receptor subtypes modulating primary afferent input to deep dorsal horn neurons in the neonatal rat

Garraway

Hochman

2001

British J Pharmacology

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1 Spinal cord slices and whole-cell patch clamp recordings were used to investigate the eects of serotonergic receptor ligands on dorsal root-evoked synaptic responses in deep dorsal horn (DDH) neurons of the neonatal rat at postnatal days (P) 3 ± 6 and P10 ± 14. 2 Bath applied 5-hydroxytryptamine (5-HT) potently depressed synaptic responses in most neurons. Similarly, the 5-HT 1/7 receptor agonist, 5-carboxamidotryptamine (5-CT) depressed synaptic responses. This action was probably mediated by 5-HT 1A receptor activation, since it occurred in the presence of the 5-HT 7 receptor antagonist clozapine and was not observed in the presence of NAN-190, a 5-HT 1A receptor antagonist. In the absence of any agonist, 5-HT 1A receptor antagonists often facilitated synaptic responses, suggesting that there is sucient endogenous 5-HT to tonically activate 5-HT 1A receptors. 3 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), the 5-HT 1A/7 receptor agonist, facilitated synaptic responses, an action probably mediated by 5-HT 7 receptors, since the facilitation could be reversed by subsequent application of the 5-HT 7 receptor antagonist clozapine. 4 Agonists for the 5-HT 1B , 5-HT 2 and 5-HT 3 receptors exerted only modest modulatory actions. 5 A pharmacological analysis of the depression evoked by 5-HT suggested an action partly mediated by 5-HT 1A receptor activation, since antagonism of the 5-HT 1A receptor with NAN-190 or WAY-100635 partly reversed 5-HT-evoked depression. In comparison, 5-HT 7 receptor activation could account for much of the 5-HT-evoked facilitation. 6 We conclude that 5-HT is capable of modulating sensory input onto DDH neurons via several receptor subtypes, producing both facilitatory and depressant actions. Also, the actions of most receptor ligands on the evoked responses were similar within the ®rst 2 postnatal weeks.

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5-HT3 receptor binding sites are on capsaicin-sensitive fibres in the rat spinal cord

Cited by 176 publications

References 32 publications

Preclinical and Early Clinical Investigations Related to Monoaminergic Pain Modulation

Preclinical and Early Clinical Investigations Related to Monoaminergic Pain Modulation

L’administration prophylactique d’ondansétron ne réduit pas l’incidence de prurit induit par le sufentanil intrathécal

Pharmacological characterization of serotonin receptor subtypes modulating primary afferent input to deep dorsal horn neurons in the neonatal rat

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