American Pain Society's 27th Annual Scientific Meeting (May 8 – 10, 2008): Peripheral Mechanisms Underlying Muscle Pain

Muscle pain is a major problem costing billions of dollars in lost wages and health care. The biological mechanisms that generate and maintain muscle pain are poorly understood but likely include peripheral and central mechanisms. Muscle pain is distinctly different from cutaneous pain because it results in longer lasting, more diffuse, poorly localized pain. This symposia will highlight recent research on peripheral mechanisms underlying muscle pain. Dr. Light will talk about the molecular receptors localized on primary sensory neurons innervating skeletal muscle, and how they synergize to detect physiological concentrations of combinations of metabolites produced by contracting muscle. Unique combinations of these receptors allow for detection of very low concentrations of these metabolites associated with the exercise pressor reflex, while other combinations are more suited to detecting metabolite levels associated with painful muscle ischemia. These molecular receptors are quite plastic and increase in conditions such as delayed onset muscle soreness (DOMS) and muscle inflammation. The same receptors are also found on circulating leukocytes and also display plasticity caused by exercise and may play a role in initiation and enhancement of muscle pain in various syndromes. Dr. Ambalavanar will discuss the role of calcitonin gene-related peptide (CGRP) in craniofacial muscle pain. Neuropeptides CGRP and substance P (SP) are expressed in trigeminal ganglion muscle primary afferent neurons and are upregulated following muscle inflammation. Administration of a CGRP receptor antagonist attenuates nocifensive behavioral responses evoked by muscle inflammation. The ATP receptor P2X3 is found on CGRP and SP muscle afferent neurons and P2X3 expression increases following muscle inflammation. Since CGRP enhances P2X3 receptor current and stimulates trafficking of P2X3 receptor to the cell membrane, CGRP antagonists are likely to block sensitization of P2X3 receptors and thus should be highly efficacious for treating deep tissue pain. Dr Cairns will discuss research that has been undertaken to examine the effects of intramuscular injection of Nerve Growth Factor NGF on healthy humans and in animal models. Injection of NGF into the jaw closer (masseter) muscle in humans causes little or no spontaneous pain but induces a mechanical sensitization limited to the injection site as well as pain during chewing and mouth opening that can last for a period of days to weeks. Current animal studies suggest that the localized effect of NGF may be mediated, in part, through peripheral mechanisms that involve mechanical sensitization of masseter muscle nociceptors without inflammation.