The role of VR1 receptors in the brain

The presence of the noxious heat-gated VR1 cation channel seems to have a well-defined functional relevance in nociceptors in contrast to VR1 positive neurons in different areas of the brain (Mezey et al., 2000). A high incidence of warm sensors in the preoptic area and the scattered high Q10 units in the midbrain and brain stem have a lower temperature threshold than the cloned VR1 receptors. Threshold temperature of warm-sensitive neurons in rat hypothalamic slices at single patches was 37.2 ± 1.8°C (Hori et al., 1999). The following list of evidence suggests that capsaicin stimulates and then desensitizes the medial preoptic warm sensors in the hypothalamus (Szolcsanyi, 1982, 1983; Hori, 1984; Pierau et al., 1986).

1 Microinjection of capsaicin into the preoptic area of rat and rabbit (a) elicits an immediate, coordinated heat loss response with vasodilatation and inhibition of shivering; and (b) excites the majority of warm units and decreases the firing rate of the cold ones.

2 After microinjection of capsaicin into the preoptic area (a) the impairment of regulatory responses to heat load (rat, cat) ensues, while the behavioural heat loss response is slightly affected; and (b) fall in body temperature to s.c. injection of capsaicin is reduced.

3 Systemic application of capsaicin excites the warm units and inhibits the responsiveness of cold units in the preoptic area.

4 After sensory desensitization induced by systemically applied capsaicin

(a) heat loss response with inhibition of shivering evoked by local heating the preoptic area is reduced;

(b) heat loss response to microinjection of capsaicin into the preoptic area is abolished;

(c) the proportion of warm and cold units in the preoptic area is reduced by about 50%;

(d) long-lasting similar ultrastructural changes are present in small cell types of neurons in the preoptic area and dorsal root ganglia.

5 After preoptic lesions, the fall in body temperature elicited by subcutaneous capsaicin injection is diminished but not abolished.

6 Birds are highly resistant to the effects of capsaicin, both on nociception and temperature regulation.

With the aid of immunohistochemical detection of VR1 receptor, mRNA of VR1, or by using VRl-null mutant mice, further novel approaches have been discovered to reveal the role of VR1 in the effect of capsaicin on warm sensors. The above series of experimental approaches might also serve as a guideline for versatile approaches which can be utilized in further research to form a thorough functional basis for the putative roles of VR1 positive neurons in the brain.

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