Role of intracellular calcium in acute thermal pain perception

Abstract

The role of intracellular calcium in acute thermal nociception was investigated in the mouse hot-plate test. Intracerebroventricular (i.c.v.) administration of TMB-8, a blocker of Ca ++ release from intracellular stores, produced hypernociception. By contrast, i.c.v. pretreatment with thapsigargin, a depletor of Ca ++ intracellular stores, produced an increase of the mouse pain threshold. Furthermore, non-analgesic doses of thapsigargin prevented the hypernociception produced by TMB-8. In mice undergoing treatment with heparin, an InsP 3 -receptor antagonist, or ryanodine, a ryanodine receptor (RyR) antagonist, a dosedependent reduction of the pain threshold was observed. Pretreatment with d-myo inositol, compound which produces InsP 3 , and 4-chloro-m-cresol, a RyR agonist, induced an antinociceptive effect. The heparin hypernociception was prevented by d-myo inositol, but not by l-myo inositol, used as negative control. In the same experimental conditions, the antinociception induced by d-myo inositol was prevented by a non-hyperalgesic dose of heparin. Similarly, the reduction of pain threshold produced by ryanodine was reversed by non-analgesic doses of 4-chloro-m-cresol, whereas the antinocicpetion induced by 4-chloro-m-cresol was prevented by non-hyperalgesic doses of ryanodine. The pharmacological treatments employed did not produce any behavioral impairment of mice as revealed by the rota-rod and hole-board tests. These results indicate that a variation of intracellular calcium contents at a supraspinal level is involved in the modulation of acute thermal nociception. In particular, the stimulation of both InsP 3 -and Ry-receptors appears to play an important role in the induction of antinociception in mice, whereas a blockade of these receptors is involved in an hypernociceptive response to acute thermal pain. #

Different involvement of type 1, 2, and 3 ryanodine receptors in memory processes

“…Conversely to ryanodine, this effect was obtained when 4-CmC was administered 30 min before the training test. This discrepancy can be explained considering that it has been observed that the antinociceptive (Galeotti et al 2004b) and depressant-like (Galeotti et al 2006) effects produced by 4-Cmc became significant starting from 90 min after administration. Taking into account this latency to produce its pharmacological effects, the action of 4-Cmc on memory processes might appear approximately in correspondence to the ryanodine effect.…”

“…In ryanodine time-course experiments, longer latencies from the training session (30, 60 min) were not used, since, conversely to 4-Cmc, it is endowed with a short lasting effect, as observed in previous behavioral experiments performed in our laboratory (Galeotti et al 2004b(Galeotti et al , 2006. From time-course experiments the ideal time of administration of 4-Cmc (30 min before training) and ryanodine (immediately after training) was chosen to perform dose-response curves.…”

Olive (Olea europaea L.) leaf extract elicits antinociceptive activity, potentiates morphine analgesia and suppresses morphine hyperalgesia in rats

“…Several investigators have reported that calcium ion has a physiological role in the regulation of pain sensitivity, and inhibition of calcium movement contributes to antinociception (Galeotti et al, 2004;Weiss and De Waard, 2006). Furthermore, L-type Ca 2+ channel antagonists produce analgesia after peripheral and central administration (Miranda et al, 1993;Esmaeili-Mahani et al, 2006).…”

Roles of ryanodine receptors in the central nervous system

“…Sitozolik Ca +2 'daki azalma, termal ağrili stimüluslara hipersensitif durum oluştururken, hücre içi Ca +2 artmasi ağri eşiğini artirmaktadir. Farelerde intraserebroventriküler ryanodin enjeksiyonu doza bağimli bir şekilde ağri eşiğini düşürmektedir [16]. Bununla beraber, RyR3'ün, RyR1'e kiyasla muskarinik analjezide büyük öneme sahip olduğu gösterilmiştir [17].…”