The capsaicin receptor TRPV1 (transient receptor potential vanilloid 1) has been an object of intense interest for pharmacological development on account of its critical role in nociception. In the course of structure activity analysis, it has become apparent that TRPV1 ligands may vary dramatically in the rates at which they interact with TRPV1, presumably reflecting differences in their abilities to penetrate into the cell. Using a fast penetrating agonist together with an excess of a slower penetrating antagonist, we find that we can induce an agonist response of limited duration and, moreover, the duration of the agonist response remains largely independent of the absolute dose of agonist, as long as the ratio of antagonist to agonist is held constant. This general approach for limiting agonist duration under conditions in which absolute agonist dose is variable should have more general applicability.
Capsaicin ; Ligands ; Nociception

Pericranial myofascial tenderness is a common phenomenon in primary headache. Nociception from pericranial muscles may play a role in provoking or aggravating headaches. Conversely, the central mechanisms of headache are also important in myofascial headaches. Myofascial headaches resulting from pericranial musculoskeletal dysfunction may stem from the referred pain caused by central convergence and facilitation. This review comprehensively evaluates myofascial headache in comparison with other primary headaches.
Headache ; Muscles ; Nociception ; Pain, Referred

Nociception is one of the most complex senses that is affected not only by external stimulation but also internal conditions. Previous studies have suggested that circadian rhythm is important in modulating nociception. REV-ERBα knock-out (KO) mice have disrupted circadian rhythm and altered mood-related phenotypes. In this study, we examined the role of REV-ERBα in inflammatory nociception. We found that the nociceptive sensitivity of KO mice was partially enhanced in mechanical nociception. However, this partial alteration was independent of the circadian rhythm. Taken together, deletion of REV-ERBα induced a mild change in mechanical nociceptive sensitivity but this alteration was not dependent on the circadian rhythm.
Animals ; Circadian Rhythm ; Mice ; Mice, Knockout* ; Nociception ; Phenotype

No abstract available.
Animals ; Capsaicin* ; Hot Temperature* ; Nociception* ; Peripheral Nerves* ; Rats*

Transient receptor potential (TRP) channels, a large family of receptor channel proteins, initially attracted researchers in the pain field as key molecules in nociception, but later they became known as more general transducer molecules for various physical stresses. In this review, I will discuss their roles in thermal and mechanical sensation, and then consider their contribution to physiological pain.
Humans ; Nociception ; Proteins ; Sensation ; Transducers ; Transient Receptor Potential Channels

Cholecystokinin is known to be involved in the modulation of nociception and to reduce the efficacy of morphine analgesia. This study investigated the effects of intrathecal administration of morphine and the cholecystokinin type B antagonist CI-988 on below-level neuropathic pain after spinal cord injury in rats. We also examined the interaction of morphine and CI-988 in the antinociceptive effect. Both morphine and CI-988 given individually increased the paw withdrawal threshold to mechanical stimulation in a dose-dependent manner. The combination of ineffective doses of intrathecally administered CI-988 and morphine produced significant analgesic effects and the combination of effective doses resulted in analgesic effects that were greater than the sum of the individual effects of each drug. Thus, morphine showed a synergistic interaction with CI-988 for analgesia of central neuropathic pain.
Analgesia ; Animals ; Cholecystokinin ; Morphine* ; Neuralgia* ; Nociception ; Rats* ; Spinal Cord Injuries*

Intraplantar injection of melittin has been known to induce sustained decrease of mechanical threshold and increase of spontaneous flinchings. The present study was undertaken to investigate how the melittin-induced nociceptive responses were modulated by changes of metabotropic glutamate receptor (mGluR) activity. Changes in paw withdrawal threshold (PWT), number of flinchings and paw thickness were measured at a given time point after injection of melittin (10microgram/paw) into the mid-plantar area of rat hindpaw. To observe the effects of mGluRs on the melittin-induced nociceptions, group I mGluR (AIDA, 100microgram and 200microgram), mGluR1 (LY367385, 50microgram and 100microgram) and mGluR5 (MPEP, 200microgram and 300microgram) antagonists, group II (APDC, 100microgram and 200microgram) and III (L-SOP, 100microgram and 200microgram) agonists were intrathecally administered 20 min before melittin injection. Intraplantar injection of melittin induced a sustained decrease of mechanical threshold, spontaneous flinchings and edema. The effects of melittin to reduce mechanical threshold and to induce spontaneous flinchings were significantly suppressed following intrathecal pre-administration of group I mGluR, mGluR1 and mGluR5 antagonists, group II and III mGluR agonists. Group I mGluR antagonists and group II and III mGluR agonists had no significant effect on melittin-induced edema. These experimental findings indicate that multiple spinal mGluRs are involved in the modulation of melittin-induced nociceptive responses.
Animals ; Edema ; Melitten ; Nociception ; Rats ; Receptors, Metabotropic Glutamate

Transient receptor potential (TRP) protein is a superfamily of cation channels which have 6 transmembrane domains and mainly pass calcium ion through themselves. There are seven types of subfamilies in the TRP superfamily. TRP channels can be activated by various kinds of stimuli. Some TRP channels are polymodal receptors because two or more types of stimuli can activate the same type of TRP channels. TRP proteins can play roles in a living organism as receptors for sensing outside stimuli or inside local stimuli of itself, as signal conductors, or as signal transducers. Especially, TRP channels have key roles in thermosensation, mechanosensation, taste, trigeminal olfaction and nociception. Therefore, TRP channels can be important subjects of research in ENT field.
Calcium ; Ion Channels ; Nociception ; Nociceptors ; Proteins ; Smell ; Thermoreceptors ; Transducers

The periaqueductal gray (PAG) is a complex mesencephalic structure involved in the integration and execution of active and passive self-protective behaviors against imminent threats, such as immobility or flight from a predator. PAG activity is also associated with the integration of responses against physical discomfort (e.g., anxiety, fear, pain, and disgust) which occurs prior an imminent attack, but also during withdrawal from drugs such as morphine and cocaine. The PAG sends and receives projections to and from other well-documented nuclei linked to the phenomenon of drug addiction including: (i) the ventral tegmental area; (ii) extended amygdala; (iii) medial prefrontal cortex; (iv) pontine nucleus; (v) bed nucleus of the stria terminalis; and (vi) hypothalamus. Preclinical models have suggested that the PAG contributes to the modulation of anxiety, fear, and nociception (all of which may produce physical discomfort) linked with chronic exposure to drugs of abuse. Withdrawal produced by the major pharmacological classes of drugs of abuse is mediated through actions that include participation of the PAG. In support of this, there is evidence of functional, pharmacological, molecular. And/or genetic alterations in the PAG during the impulsive/compulsive intake or withdrawal from a drug. Due to its small size, it is difficult to assess the anatomical participation of the PAG when using classical neuroimaging techniques, so its physiopathology in drug addiction has been underestimated and poorly documented. In this theoretical review, we discuss the involvement of the PAG in drug addiction mainly via its role as an integrator of responses to the physical discomfort associated with drug withdrawal.
Amygdala ; Humans ; Morphine ; Nociception ; Periaqueductal Gray ; Substance-Related Disorders

BACKGROUND: Cannabinoids have shown antinociceptive action. The aims of this study were to examine the effect of chronic infusion of a cannabinoids receptors agonist (WIN 55, 212-2) for thermal nociception at the spinal level, and to also observe the development of toxicity. METHODS: Male Sprague-Dawley rats were implanted with lumbar intrathecal catheters with the nociceptive response (withdrawal response latency) determined by exposing the plantar surface of the hindpaw to radiant heat. Initially, the effect of intrathecal WIN 55, 212-2 was evaluated followed by the change in the effect at 1, 2, 3 and 4 weeks after repeated infusion. Finally, the histopathological findings were assessed 1 and 4 weeks following the infusion of WIN 55, 212-2. RESULTS: Intrathecal WIN 55, 212-2 was found to produce a limited antinociception during the thermal test. %MPE of WIN 55, 212-2 at 1, 2, 3, and 4 weeks after infusion was not different from each other. No abnormal pathological findings were observed following a chronic intrathecal infusion of WIN 55, 212-2. CONCLUSIONS: WIN 55, 212-2, a cannabinoids receptors agonist, may be useful in the management of thermal nociception, without changing the effectiveness or causing the toxicity following a chronic infusion at the spinal level.
Animals ; Cannabinoids* ; Catheters ; Hot Temperature ; Humans ; Male ; Nociception ; Rats* ; Rats, Sprague-Dawley