Trends in Neurosciences
ReviewBrain Circuits Encoding Reward from Pain Relief
Section snippets
Relief of Pain Is a Reward
Substantial scientific progress in the past century has deepened our understanding of somatosensation, including the neurobiology of pain that often follows from activation of nociceptors 1, 2. Pain is commonly categorized along with other sensations and relief of pain is thus often interpreted simply as termination of nociceptive transmission. Early Greek philosophers, however, grouped pain with emotions and appetites rather than sensation. Pain was considered to be the opposite of pleasure [3]
Mesolimbic Dopaminergic Responses to the Onset and Offset of Pain
Mesolimbic dopamine neurons are well recognized for their responses to primary rewards and reward-predicting cues, as well as for their role in approach behavior, learning, reinforcement, decision making, and the expression of positive emotions such as pleasure and happiness (reviewed in 13, 14, 15). Electrophysiological characterization of midbrain dopamine neurons in monkeys and rodents has established that, in addition to tonic neural activity, most neurons display phasic activations
Brain Activity in Response to Pain and Pain Relief
Major advances in elucidating the brain mechanisms of pain have been achieved using neuroimaging techniques in humans and animals. BOLD fMRI studies identified brain regions frequently activated by acute noxious stimulation, including the thalamus, the primary and secondary somatosensory cortices (S1, S2), the mid/posterior insula, and the ACC [36]. These regions interact with a broad network of corticolimbic structures encoding reward/motivation-related information to shape behavioral
Role of Endogenous Opioid Circuits in Pain and Pain Relief
Earlier studies with opioid antagonists established a critical role of the endogenous opioid system for innate analgesia during traumatic and stressful situations and during ‘runner's high’ 52, 53. ACC neurons express high levels of endogenous opioid neuropeptides and their receptors [54], suggesting that at least part of the endogenous analgesic effects could be mediated by opioid activity in this region [55]. Interestingly, in rats systemic administration of morphine is able to inhibit
Relief of Pain Provides a Motivational and Learning Signal
A series of studies conducted in Drosophila, rodents, and humans was implemented to investigate the mechanisms of learning associated with the relief of pain (reviewed in [59]). To assess both fear and relief conditioning, these studies used a paradigm in which a conditioning stimulus either preceded or followed a brief noxious electric shock, respectively. In Drosophila, when a neutral olfactory cue preceded the foot shock (fear conditioning), the odor acquired aversive conditioned valence.
NAc Dopamine Signaling and Relief of Ongoing Pain
The pain-relief signals discussed above have employed paradigms involving the rapid offset of an acute noxious stimulus. Given the known reorganization of brain circuits in chronic pain, it is important to determine whether relief of ongoing or chronic pain analogously produces a motivationally salient pain-relief signal and how this signal is mediated. This was investigated in rodent models of ongoing or chronic pain using the conditioned place preference (CPP) learning paradigm. Relief of
Opioid Signaling in the ACC and Relief of Ongoing Pain
Because endogenous as well as administered opioids are able to inhibit nociceptive neurons in the ACC, it is plausible to speculate that opioid activity in this region may be involved in relief of pain aversiveness and activation of the reward circuit. LaGraize et al. have demonstrated that, in neuropathic rats, microinjection of morphine into the ACC produced a selective decrease of affective/motivational aspects of pain with no alteration of the mechanical paw-withdrawal threshold [76].
Concluding Remarks: Brain Circuits for Pain-Relief Reward
In addition to nociceptive (sensory) information, the pain experience is significantly dependent on emotional and cognitive processing in the brain [50]. Onset of pain or increasing pain is a motivationally salient event that often supersedes other, competing motivational conditions to generate an appropriate behavioral response (e.g., avoidance, guarding, decreased mobility) [78]. Likewise, pain offset or reducing pain is also a motivationally relevant event leading to approach behavior. Thus,
Acknowledgments
The authors thank Professor Howard Fields, UCSF for helpful comments on the manuscript and the support of the NIDA (DA 034975).
Glossary
- Blood oxygen level-dependent (BOLD) imaging
- a technique used in fMRI that measures neuronal activity in different areas of the brain based on changes in the ratio of oxygenated to deoxygenated hemoglobin. In research, the method is used to determine which regions of the brain are activated during a specific task such as during the application of a painful stimulus.
- Conditioned place preference (CPP)
- an operant learning paradigm used to evaluate the motivational effects of different experiences in
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