Electrical stimulation of the gastrocnemius muscle in the spontaneously hypertensive rat increases the pain threshold: role of different serotonergic receptors

In a previous study, prolonged low-frequency muscle stimulation in the hind leg of the fully conscious spontaneously hypertensive rat (SHR) was shown to induce a long-lasting reduction of blood pressure. It was also shown that opioid and serotonergic (5-HT) systems were involved. More recently, we have shown that the 5-HT1 receptors are involved in the post-stimulatory decrease in blood pressure. In the present study, the influence of this type of muscle stimulation on the pain threshold was investigated. Pain perception was measured as the squeak threshold to noxious electric pulses. After cessation of the stimulation, an analgesic response was elicited within 60 min and peak analgesia developed after 120 min, being 139 ±10% (P < 0.01) of the prestimulatory control value. The increased pain threshold lasted for another 2 h. One group of SHR was pretreated with PCPA, a serotonin synthesis blocker, which completely abolished the post-stimulatory analgesia. To analyse further the involvement of different serotonin systems, drugs with selective affinity for 5-HT receptors were used. In one group a prestimulatory dose of metitepine maleate (a 5-HT1&2 receptor antagonist) abolished the post-stimulatory elevation of the pain threshold. The prolonged analgesic response was still present after prestimulatory treatment with ritanserin or ICS 205–930 (5-HT2 and 5-HT3 blocking agents respectively). In another group of experiments, the serotonin receptor antagonists were administered post-stimulation to animals with fully elicited analgesia. None of the antagonists used could reverse the elevation of pain threshold towards prestimulatory levels. Thus, intact 5-HT systems were necessary to elicit the analgesia to muscle stimulation and the response was mediated by the 5-HT1 receptor. However, the results indicate that serotonin is not required to maintain the analgesia once it has been elicited.