Reward Circuitry Plasticity in Pain Perception and Modulation

Abstract

Although pain is a widely known phenomenon and an important clinical symptom that occurs in numerous diseases, its mechanisms are still barely understood. Owing to the scarce information concerning its pathophysiology, particularly what is involved in the transition from an acute state to a chronic condition, pain treatment is frequently unsatisfactory, therefore contributing to the amplification of the chronic pain burden. In fact, pain is an extremely complex experience that demands the recruitment of an intricate set of central nervous system components. This includes cortical and subcortical areas involved in interpretation of the general characteristics of noxious stimuli. It also comprises neural circuits that process the motivational-affective dimension of pain. Hence, the reward circuitry represents a vital element for pain experience and modulation. This review article focuses on the interpretation of the extensive data available connecting the major components of the reward circuitry to pain suffering, including the nucleus accumbens, ventral tegmental area, and the medial prefrontal cortex; with especial attention dedicated to the evaluation of neuroplastic changes affecting these structures found in chronic pain syndromes, such as migraine, trigeminal neuropathic pain, chronic back pain, and fibromyalgia.

Physical Activity Induces Nucleus Accumbens Genes Expression Changes Preventing Chronic Pain Susceptibility Promoted by High-Fat Diet and Sedentary Behavior in Mice

“…Indeed, we were the first to report that biological processes involved in neuroplasticity, within an HFD and sedentary behavior context, may prevent chronic pain susceptibility. In fact, several studies reported that genes implicated in the neuroplasticity in the NAc is related to chronic pain facilitation and hyperalgesia in humans and animals (Woolf, 2000;Apkarian et al, 2011;Mansour et al, 2014;Zhang et al, 2014;Kuner and Flor, 2016;DosSantos et al, 2017). However, it is important to emphasize that studies with humans from functional magnetic resonance imaging showed evidence that chronic pain and neuroplasticity are a cognitive maladaptive learning process (Apkarian et al, 2011;Mansour et al, 2014;DosSantos et al, 2017).…”

“…In fact, several studies reported that genes implicated in the neuroplasticity in the NAc is related to chronic pain facilitation and hyperalgesia in humans and animals (Woolf, 2000;Apkarian et al, 2011;Mansour et al, 2014;Zhang et al, 2014;Kuner and Flor, 2016;DosSantos et al, 2017). However, it is important to emphasize that studies with humans from functional magnetic resonance imaging showed evidence that chronic pain and neuroplasticity are a cognitive maladaptive learning process (Apkarian et al, 2011;Mansour et al, 2014;DosSantos et al, 2017). Whereas studies with animal models investigated the role of one single molecular signaling related to neuroplasticity, such as BDNF/TrkB pathway, for instance (Zhang et al, 2014(Zhang et al, , 2017Wang et al, 2017).…”

Physical Activity Induces Nucleus Accumbens Genes Expression Changes Preventing Chronic Pain Susceptibility Promoted by High-Fat Diet and Sedentary Behavior in Mice

“…In fact, we were the first to report that biological processes involved in neuroplasticity, at 11 least within an HFD-induce obesity and sedentary behavior context, may prevent the CP 12 susceptibility. Whereas several studies reported that neuroplasticity in the NAc is underlying CP in 13 humans and animals (Apkarian et al, 2011;DosSantos et al, 2017;Kuner and Flor, 2016;Woolf, 14 2000), our results may reflect an neurodegeneration process in the NAc caused by HFD and sedentary 15 behavior supporting the CP susceptibility, and secondarily, a neuroplasticity counter-regulatory 16 mechanism orchestrated by the voluntary PA. Indeed, PA and physical exercise is already known to 17 produce neuroplasticity Fernandes et al, 2017;Lourenco et al, 2019).…”

Optical Modulation on the Nucleus Accumbens Core in the Alleviation of Neuropathic Pain in Chronic Dorsal Root Ganglion Compression Rat Model

“…Chronic neuropathic pain is a devastating condition associated with maladaptive neural circuits in the brain. Abundant factors and neural circuits contribute to the experience of pain . The optical modulation of brain structures impacts both physical and emotional aspects of pain , which confirms the optogenetic approach in the control of pain perception .…”