New developments in the understanding of the pathophysiology of muscle pain

Objectives: The review gives an overview of recent data on spinal mechanism s of muscle pain obtained in animal experiments. Possible parallels between these data and symptoms in patients with muscle pain are discussed. Findings: The afferent input from inflamed muscle activates neurokinin-1 [N K-1] and N-methyl-D-aspartate [NMDA] receptors in the spinal cord, which le ads to hyperexcitability of dorsal horn neurons. Simultaneously, the backgr ound activity in some spinal segments rose. During longer-lasting lesions, the excitability and background activity of the neurons changed independent ly from each other. After 12 d of a myositis the excitability of the neuron s began to return to normal values, whereas the background discharge contin ued to increase. The substance P [SP] content of the dorsal horn remains ap proximately constant during acute and subacute myositis, i.e., the decrease of neuronal excitability during persistent myositis occurs in spite of an unchanged SP content. In the reported studies, nitric oxide [NO] was found to be not involved in the control of excitability of dorsal horn neurons. However, NO had a stron g action on the background activity of the cells. The spinal neurons that s ynthesize NO react in a sensitive and differential way to muscle lesions. F ollowing a lesion the number of the NO cells first increases and then decre ases with a time-course that depends on the frequency of the C-fiber input and hence on the severity of the lesion. Conclusions: Afferent input from a damaged muscle is very effective in indu cing neuroplastic changes [hyperexcitability and increase in background act ivity] in sensory neurons of the spinal cord. The hyperexcitability is assu med to cause hyperalgesia in patients; the background activity, spontaneous pain. The data suggest that during sub-acute myositis the hyperalgesia dec reases, whereas spontaneous pain increases more and more. The enzymatic act ivity of NO synthesizing neurons is strongly influenced by a muscle lesion. As NO is one of the main factors that controls the background activity of nociceptive spinal neurons, these cells are likely to determine the degree of spontaneous pain in an awake individual.