Excitatory effects of 5-hydroxytryptamine, histamine and potassium ions on muscular group IV afferent units: a comparison with bradykinin.

The hypothesis that different receptor sites for algesic agents exist at free nerve endings in skeletal muscle has been tested by administering bradykinin and 5-hydroxytryptamine (5-HT) repeatedly in anaesthetized cats and evaluating the response behaviour of single group IV afferent units from the gastrocnemius-soleus muscle. Repeated intraarterial administration of bradykinin at intervals of 1 and 2 min usually elicited fibre responses without tachyphylaxis. Injections of equieffective doses of 5-HT, however, given in the same manner evoked fibre reactions that were strongly tachyphylactic. In units responding to both bradykinin and 5-HT a refractoriness to 5-HT could be induced by repeated injections of this agent without impairing the stimulating potency of bradykinin on the same nerve ending. Such a lack of cross-tachyphylaxis seems to apply also to the effects of histamine on one side and bradykinin or 5-HT on the other. These findings suggest that bradykinin, 5-HT and probably histamine exert their excitatory action on muscular group IV afferent units via different receptor sites.

Evidence for the existence of different receptor sites for algesic agents at the endings of muscular group IV afferent units

Experiments were performed in chloralosed cats where gastric motility was recorded by the "volume method". Mucosal and serosal nociceptive stimulations were accomplished by local heating to 45-52 degrees C. Heating generally elicited gastric relaxations, mainly due to activation of extrinsic inhibitory reflexes, but mucosal heating sometimes caused contractile responses which were resistant to nicotinic and adrenergic blockade. The contractions were, however, blocked by atropine and, further, could not be demonstrated after degeneration of splanchnic afferents. On the basis of these and earlier results it is suggested that the gastric contractions induced by mucosal nociceptive stimulation are due to axon reflexes, conveyed by splanchnic afferents that, possibly via release of substance P, make non-nicotinic reflex contacts with intramural excitatory cholinergic neurons.

Atropine-sensitive gastric smooth muscle excitation by mucosal nociceptive stimulation--the involvement of an axon reflex?

Pain receptors respond to a wide range of physical and chemical stimuli. Their sensitivity is increased by inflammation. Chemical excitants of pain receptors include exogenous substances, which are foreign to the body, and endogenous substances which occur naturally in the body. Endogenous pain-producing substances include acetylcholine, HCl in gastric juice (at pH<3.0), potassium ions, 5-hydroxytryptamine, and plasma kinins, e. g. bradykinin. These may be released from ruptured cells or formed in body fluids by injury. Many endogenous chemicals may contribute to the pain of disease.

C. A. Keele

Papers

Excitants of pain receptors