Patients suffering from pain experience negative emotional states that can impact their quality of life. These maladaptive emotional states can lead to involuntary opioid overdose and other poor mental health outcomes. Uncovering the mechanisms responsible for this pain-induced negative affect could help improve a patient’s overall health.
In a paper published in the journal Neuron, NIDA-funded researchers identified a critical role for an internal brain opioid network called the dynorphin-kappa opioid receptor (KOR) system. Investigators studied this system within the brain’s nucleus accumbens, which integrates the aversive and rewarding aspects of stimuli. They discovered that activating KORs there decreases the motivation for obtaining something pleasurable, which is a characteristic feature of pain-induced negative emotion and prompts aversive behaviors in a manner similar to inflammatory pain.
Moreover, blocking these receptors in the nucleus accumbens decreases the emotional component of pain, indicating that KORs play a necessary role. They discovered that as the body senses inflammatory pain, KOR signaling is increased and dynorphin neurons in the nucleus accumbens become more excitable. They then showed that activating dynorphin neurons in that part of the brain mimics the effects of inflammatory pain on negative affect, and conversely, silencing dynorphin neurons in animals with inflammatory pain alleviates the ability of pain to produce this effect.
Together, these findings implicate the dynorphin-KOR system in the nucleus accumbens shell as mediators of the negative emotional component of inflammatory pain. These findings provide further insights into neurobiological targets for future pharmacotherapies that address unwanted negative outcomes in pain patients. In addition, emerging therapies such as focused ultrasound technology or the development of light activated compounds and drugs specifically targeting the activated kappa opioid structure could lead to selective and localized treatments.
- Nicolas Massaly; Bryan A. Copits; Adrianne R. Wilson-Poe; Lucia Hipólito; Tamara Markovic; Hye Jean Yoon; Shiwei Liu; Marie C. Balicki; Dionnet L. Bhatti; Sunil Sirohi; Brendan M. Walker; Rachael Neve; Catherine M. Cahill; Kooresh I. Shoghi; Jordan G. McCall; Robert W. Gereau, IV; Ream Al-Hasani; Michael R. Bruchas; Jose A. Morón. Pain-Induced Negative Affect Is Mediated Via Recruitment Of The Nucleus Accumbens Kappa Opioid System. Neuron.