Roles of the periaqueductal gray in descending facilitatory and inhibitory controls of intramuscular hypertonic saline induced muscle nociception

•Role of subregions of PAG in descending modulation of muscle pain was studied.•Fos expression within the subregions of PAG differs in response to muscle pain.•dl PAG participates in the descending facilitation of pain.•vl PAG is involved in the descending inhibition of pain.

Despite the importance of the periaqueductal gray (PAG) in the modulation of nociception and pain, many aspects of the roles of the different columns of the PAG in descending controls: facilitation and inhibition, are not understood. Employing a tonic muscle pain model established by i.m. injection of 5.8% saline into the gastrocnemius muscle, we now report the results of investigations designed to explore any differences in Fos expression in the different functional columns of the PAG in male Sprague–Dawley rats. In a second series of experiments, effects of the PAG on descending control of spinally-organized nociception were assessed by measuring hind paw withdrawal reflexes to noxious mechanical and heat stimulation before and after electrolytic lesion of specific columns of the PAG. Our results show that Fos expression within different columns of the PAG increases significantly and differentially following i.m. injection of 5.8% saline. The mean number of Fos positive neurons in the dorsolateral (dl), lateral (l), dorsomedial (dm) PAG elicited by i.m. injection of 5.8% saline reached a peak at 4 h with a gradual decrease over time, whereas the maximum number of Fos-positive neurons in the ventrolateral (vl) PAG was observed 8 h after i.m. injection. Contralateral lesion of the dl PAG significantly depressed ipsilateral secondary mechanical hyperalgesia in intramuscularly induced (5.8% saline) nociception (P < 0.05), whereas heat hypoalgesia was not affected (P > 0.05). By contrast, contralateral lesion of the vl PAG completely blocked the occurrence of ipsilateral heat hypoalgesia (P < 0.05), while bilateral mechanical hyperalgesia was unaffected (P > 0.05). In conclusion, functions of specific columns of the PAG in the control of spinal nociceptive activities are not homogeneous. It is suggested that, in this muscle pain model, the dl PAG and vl PAG participate in descending facilitation and inhibition of nociception, respectively.