Caffeine induces central cholinergic analgesia

Abstract

The antinociceptive effect of caffeine was examined by using the hot-plate, abdominal constriction tests in mice and the tail flick and paw-pressure tests in rats. Caffeine (1-5 mg kg -1 s.c. in mice; 2.5-5 mg kg -1 i.p. in rats) produced significant antinociception in both species which was prevented by atropine (5 mg kg -1 i.p.), pirenzepine (0.1 µg per mouse i.c.v.), hemicholinium-3 (1 µg/ mouse i.c.v.) and N 6 -cyclopentyladenosine (5 µg/mouse i.c.v.), but not by naloxone (1 mg kg -1 i.p.), CGP 35348 (100 mg kg -1 i.p.), α-methyl p-tyrosine (100 mg kg -1 i.p.) and reserpine (2 mg kg -1 i.p.). Intracerebroventricular injection of caffeine in mice at doses (2.5-5 µg per mouse) which were largely ineffective by parenteral routes, induces an antinociception whose intensity equalled that obtainable s.c. or i.p. In the antinociceptive dose-range, caffeine did not produce any behavioural impairment as revealed by the rotarod and Irwing tests. On the basis of the above data, it can be postulated that caffeine exerts an antinociceptive effect mediated by central amplification of cholinergic transmission.

Ryanodine receptors are involved in muscarinic antinociception in mice

“…It should also be taken into account that compounds able to activate RyR, such as caffeine, are endowed with central antinociceptive properties [10,26,29].…”

Nutrient intake in women with primary and secondary Sjögren's syndrome

“…Similarly, the heightened intake of caffeine in the 1 SS group may be related to greater coffee, tea and=or soda intake, in an attempt to attenuate the dry mouth sensation. Interestingly, caffeine has anti-nociceptive properties (Kraetsch et al, 1996;Ghelardini et al, 1997), which may alleviate oral pain. Caffeine may also reduce fatigue, which is a predominant symptom in Sjögren's syndrome (Homma et al, 1994).…”

“…Caffeine may also reduce fatigue, which is a predominant symptom in Sjögren's syndrome (Homma et al, 1994). Moreover, caffeine is known to amplify cholinergic transmission (Ghelardini et al, 1997), which could theoretically stimulate salivary secretion. The greater intake of supplemental calcium in women with 2 SS=SLE might be due to clinical advice.…”

Modulation of paracetamol antinociception by caffeine and by selective adenosine A2 receptor antagonists in mice

“…In mice, rats and humans caffeine increases the antinociceptive effects of paracetamol (Laska et al, 1983;Granados-Soto et al, 1993;Engelhardt et al, 1997). When used alone caffeine has been shown to cause antinociception in rats and mice (Sawynok et al, 1995;Ghelardini et al, 1997;AboSalem et al, 2004).…”