Neuropathic pain induces sensory and affective disordersImplication of the noradrenergic system/implicación del sistema noradrenérgico en los desórdenes afectivo-sensoriales inducidos por el dolor neuropático

Abstract

Pain is an essential physiological mechanism for the survival. However, maintained painful states may derive in pathological conditions with emotional, affective, and social implications that constitute a source of personal suffering. Epidemiological and preclinical studies have supported comorbidity between chronic pain and mood disorders such as depression and anxiety, suggesting common neurobiological mechanisms. The knowledge of the underlying bases of these processes would help to develop new therapeutic approaches that improve the diagnosis and treatment of patients. Indeed, the aim of this thesis was to study the molecular, behavioural and neurological mechanisms subjacent to chronic pain from two points of view. On the one hand, we investigated the function of noradrenergic locus coeruleus nucleus as an essential regulator of ascending and descending pain pathways. In this sense, although several studies have reported the participation of the locus coeruleus in acute pain, its role on chronic pain remains unclear. On the other hand, we analyzed the effect of antidepressant treatment on sensorial and affective dimensions of pain. The findings obtained showed that neuropathic pain produced a significant and stable decrease in the pain threshold, coupled to an anxiogenic and depressive-like states over the time. Emotional changes temporally coincided with marked modifications at noradrenergic locus coeruleus level, such as alterations in tyrosine hydroxylase and noradrenaline transporter expressions, alpha2-adrenoceptor sensitivity, locus coeruleus firing activity and noradrenaline release. In addition, nerve-injury disrupts the responsiveness of locus coeruleus to noxious stimulation from early stages of neuropathy. These behavioural and noradrenergic alterations were restored and/or blocked after treatment with analgesic antidepressants. These results might contribute to provide new putative noradrenergic targets for future therapeutic approaches.