Differential expression of µ-, δ-, and κ-opioid receptors in muscle afferents from male and female rats.

Small diameter unmyelinated (group IV) and myelinated (group III) muscle afferents transmit action potentials to signal muscle pain and the exercise pressor reflex (EPR). The EPR helps to drive the cardiovascular response to exercise. µ- (µOR), δ- (δOR), and κ- (κOR) opioid receptors (OR) have been shown to be expressed by dorsal root ganglia (DRG) neurons, but only peripheral µOR activation has been shown to inhibit the EPR mediated by group IV afferents. To determine if this results from differential OR expression, we identified group IV neurons in DRG and axons in gastrocnemius muscles from both male and female rats, and used immunocytochemistry to compare the expression of µOR, δOR, and κOR. We show that µOR labeling was more frequently observed in group IV somata and axons vs. δOR or κOR. OR axonal labeling was lower than somata labeling, particularly for δOR & κOR. There were no significant differences in OR staining between male and female animals. The relatively high µOR axonal expression suggests that µOR are selectively transported to the peripheral group IV axons and can explain the selective effect of µOR agonists to inhibit group IV afferent activity that generates the EPR and muscle pain.