Increased sensitivity of group III and group IV afferents from incised muscle in vitro

Understanding deep muscle pain is of increasing importance for evaluating clinical pathologic pain states. Previously, a central role of deep muscle tissue in the development of ongoing pain behavior after incision was demonstrated. The underlying mechanisms, however, remain unclear. Using a new in vitro plantar flexor digitorum brevis (FDB) muscle-nerve preparation, we investigated properties of mechanosensitive group III and IV afferents innervating incised and unincised muscle, and explored potential mediators of afferent excitation after incision. Afferents of uninjured muscle had a low incidence (14.3%) of ongoing activity. A high proportion (65.8%) of afferents responded to heat and a minority, 20.8%, were activated by pH 6.0 lactic acid. Incision increased the prevalence of afferents with ongoing activity to 54.7%. A greater proportion of group III and IV afferents responded to pH 6.0 lactic acid after incision compared to control (55.4% vs. 20.8%). Sensitization of afferents to heat and mechanical stimulation was prominent in group IV afferents after incision; both heat (38.0 vs. 40.5°C in control) and mechanical response threshold (median: 5.0 vs. 22.0 mN in control) were decreased. The finding hat incision increased ongoing activity of muscle afferents is consistent with our previous in vivo studies and supports the idea that deep muscle tissue has a prominent role in the genesis of ongoing pain after incision. The enhanced chemosensitivity of muscle afferents to lactic acid after incision suggests an increased response to an ischemic mediator that may contribute to pain and hyperalgesia caused by surgery in deep tissues.