THE ROLE OF KAPPA OPIOID RECEPTORS IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS ON THE AFFECTIVE AND SENSORY COMPONENTS OF CHRONIC NEUROPATHIC PAIN IN MICE

Abstract

Chronic pain is a widely recognized debilitating condition worldwide that has been associated with disrupted sleep and increased usage of opioids to relieve pain. Our laboratory has interest in exploring the role of kappa opioid agonists and receptors (KOR) signaling in chronic pain. One area that has been brought to our attention is the KOR signaling in the paraventricular nucleus (PVN) which may play a key role in promoting pain and management of it. Our primary aim is to investigate the role of KOR neurons in the PVN on the affective and sensory components of chronic pain induced by partial sciatic nerve ligation (PSNL) surgery in male mice. Secondary aims propose to (a) evaluate the systemic blocking of KOR signaling using the KOR antagonist, nor-Binaltorphimine (nor-BNI) on the affective and sensory components of pain as well as (b) to evaluate the consequences of specific blockade of KOR in the PVN using KOR CRISPR/Cas9 gene editing technology on the affective and sensory components of pain and (c) potential consequences of KOR manipulations on learning process. Our data demonstrate that systemic and local (PVN) blockade of KOR neurons blocked conditioned place preference (CPP) to an analgesic drug without affecting learning behavior, suggesting that PVN-KOR may play a role not only in sleep, but also in the affective component associated with chronic pain. Thus, KOR blockade in the PVN might diminish the aversive component of chronic pain and additionally contribute to the restoration of sleep in the PSNL mice