Peripheral nerve injury attenuates stress-induced Fos-family expression in the Locus Coeruleus of male Sprague-Dawley rats.

The ability to cope with acute stressors is impaired in people with chronic neuropathic injuries. The regulation of stress coping responses depends critically on several parallel interconnected neural circuits, one of which originates in the Locus Coeruleus. In rats, chronic constriction injury (CCI) and acute stress each modulate noradrenergic activity of the Locus Coeruleus (LC) although with different temporal patterns. This study investigated the effects of CCI on the neuronal activity of the LC to acute restraint stress using the immunohistochemical detection of Fos-family protein expression. Male Sprague-Dawley rats underwent CCI surgery and 11 days later were restrained for 15 min. The number and location of single-labelled neurons (c-Fos, FosB/ΔFosB and tyrosine hydroxylase (TH) immunoreactive) neurons and double labelled neurons (c-Fos, or FosB/ΔFosB with TH) were quantified for the LC and surrounding regions. Comparisons were made with rats that underwent sham surgery or anaesthesia (20 min). Restraint triggered a struggling response in all rats. CCI attenuated restraint-induced Fos expression in LC neurons. A significant proportion (30-50%) of these LC Fos positive neurons did not contain TH. These data suggest that nerve injury might impair the ordinary cellular response of the LC to an acute stress. The association of stress-related disorders in people with neuropathic injuries suggests that the observations made in this study may reflect a part of the mechanism underlying these clinical comorbidities.