Effect of buspirone on thermal sensory and pain thresholds in human volunteers

The effects of buspirone (30 mg p.o.) on thermal sensory and pain thresholds were investigated in twelve female volunteers (26 ± 2 yrs) in a prospective, randomized, double-blind, double-dummy, placebo-controlled study with morphine (10 mg i.v.) as positive control.Morphine significantly increased the heat pain detection threshold (ΔT: placebo 1.0°C and 1.3°C, p < 0.05) at 60 minutes. Buspirone caused mild sedation in six participants at 60 minutes, but was without effect on any of the measured parameters.Buspirone in the maximal recommended dose was without significant effect on thermal pain. However, as it is only a partial agonist at the 5-HT1A receptor and also acts on other receptor types, the negative results of the present study do not rule out a possible analgesic effect of more specific 5-HT1A receptor agonists.Numerous animal studies have implicated serotonergic pathways, particularly the 5-HT1a receptors, in pain perception [1,2]. Serotonin-transporter deficient mice which have lower levels of tissue serotonin have reduced inflammatory pain and thermal hyperalgesia [3]. 5-HT1a deficient (knock-out) mice exhibit higher thermal hypersensitivity than naive, non-knock-out mice [4]. The 5-HT1a agonist 8-OH-DPAT has analgesic properties in the hot-plate and tail-flick test in mice [5]. Various other 5-HT1a agonists, including the partial agonist buspirone, also exhibit analgesic effects in the hot-plate test in mice [6] and in a rat model of surgical pain [7]. Accordingly, 5-HT1a receptor antagonists block analgesia induced by stimulation of the lateral hypothalamus [8]. The most likely mechanism is through descending inhibitory pathways that end in the dorsal horn of the spinal cord and affect sensory centripetal neurotransmission.However, serotonin agonists acting on 5-HT1a receptors have also been shown to cause hyperalgesia in rats [9,10], a finding observed by Fasmer et al. with lower doses of buspirone as well [5]. In concordance to these reports, a perip