Central modulation of pain

Ossipov, Michael H.; Dussor, Gregory; Porreca, Frank

doi:10.1172/jci43766

Cited by 888 publications

(785 citation statements)

References 146 publications

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“…One possible explanation of this local effect of ethanol is activation of the descending nociceptive facilitation pathway [47]. It is interesting to note that neuronal activity in the mPFC, especially the PrLC and ILC, can be inhibited by a GABAergic enhancing mechanism under some pathological pain conditions in animal models of joint arthritis, peripheral neuropathy, and visceral pain [14,[48][49][50].…”

Section: Involvement Of Mpfc In Top-down Facilitation Of Mechanical Pmentioning

confidence: 99%

Ethanol Increases Mechanical Pain Sensitivity in Rats via Activation of GABAA Receptors in Medial Prefrontal Cortex

Geng

Wang

et al. 2016

Neurosci. Bull.

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Ethanol is widely known for its ability to cause dramatic changes in emotion, social cognition, and behavior following systemic administration in humans. Human neuroimaging studies suggest that alcohol dependence and chronic pain may share common mechanisms through amygdala-medial prefrontal cortex (mPFC) interactions. However, whether acute administration of ethanol in the mPFC can modulate pain perception is unknown. Here we showed that bilateral microinjections of ethanol into the prelimbic and infralimbic areas of the mPFC lowered the bilateral mechanical pain threshold for 48 h without influencing thermal pain sensitivity in adult rats. However, bilateral microinjections of artificial cerebrospinal fluid into the mPFC or bilateral microinjections of ethanol into the dorsolateral PFC (also termed as motor cortex area 1 in Paxinos and Watson's atlas of The Rat Brain. Elsevier Academic Press, Amsterdam, 2005) failed to do so, suggesting regional selectivity of the effects of ethanol. Moreover, bilateral microinjections of ethanol did not change the expression of either pro-apoptotic (caspase-3 and Bax) or anti-apoptotic (Bcl-2) proteins, suggesting that the dose was safe and validating the method used in the current study. To determine whether c-aminobutyric acid A (GABA A ) receptors are involved in mediating the ethanol effects, muscimol, a selective GABA A receptor agonist, or bicuculline, a selective GABA A receptor antagonist, was administered alone or co-administered with ethanol through the same route into the bilateral mPFC. The results showed that muscimol mimicked the effects of ethanol while bicuculline completely reversed the effects of ethanol and muscimol. In conclusion, ethanol increases mechanical pain sensitivity through activation of GABA A receptors in the mPFC of rats.

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Section: Involvement Of Mpfc In Top-down Facilitation Of Mechanical Pmentioning

confidence: 99%

Ethanol Increases Mechanical Pain Sensitivity in Rats via Activation of GABAA Receptors in Medial Prefrontal Cortex

Geng

Wang

et al. 2016

Neurosci. Bull.

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“…Pain after surgery-in the aftermath of incision, intra-operative tissue damage and the ensuing inflammatory cascade-is subject to a host of psychosocial influences, including those related to mood and attention [92]. Psychosocial risk factors of particular concern with respect to CPSP include pre-surgical depression, anxiety, surgical fear [93], and emotional numbing [94].…”

Section: Psychological Predictors and Means Of Interveningmentioning

confidence: 99%

Preventive Analgesia and Novel Strategies for the Prevention of Chronic Post-Surgical Pain

Clarke

Poon

Weinrib

et al. 2015

Drugs

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Chronic post-surgical pain (CPSP) is a serious complication of major surgery that can impair a patient's quality of life. The development of CPSP is a complex process which involves biologic, psychosocial, and environmental mechanisms that have yet to be fully understood. Currently perioperative pharmacologic interventions aim to suppress and prevent sensitization with the aim of reducing pain and analgesic requirement in acute as well as long-term pain . Despite the detrimental effects of CPSP on patients, the body of literature focused on treatment strategies to reduce CPSP remains limited and continues to be understudied. This article reviews the main pharmacologic candidates for the treatment of CPSP, discusses the future of preventive analgesia, and considers novel strategies to help treat acute postoperative pain and lessen the risk that it becomes chronic. In addition, this article highlights important areas of focus for clinical practice including: multimodal management of CPSP patients, psychological modifiers of the pain experience, and the development of a Transitional Pain Service specifically designed to manage patients at high risk of developing chronic post-surgical pain. Key PointsThe development of chronic post-surgical pain (CPSP) is a complex process which involves biologic, psychosocial, and environmental mechanisms.Ketamine (an NMDA antagonist) appears to be the pharmacologic agent with the most consistent positive preventive analgesic results.The variation in patient response to pharmacologic agents can be explained, in part, by genetic polymorphisms.Understanding the heritability of CPSP will be useful when developing predictive algorithms to determine the preoperative risk for developing CPSP.Psychological treatments delivered before and after surgery have the potential to influence the trajectory of CPSP from the earliest days, in combination with multimodal, preventive analgesia.

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“…Stimulation of these descending inhibitory networks inhibits nociception [20]. Anatomical tracing methods combined with immunohistochemistry have established that a large proportion of neurons in the rostral ventromedial medulla (RVM) that project to lamina I-IIo and IV-V of the spinal cord are GABAergic/glycinergic [21,22].…”

Section: Glycine Neurotransmission and Chronic Painmentioning

confidence: 99%

“…Kato et al [23] used in vivo patch recording to demonstrate that partially overlapping, monosynaptic GABAergic and glycinergic pathways from RVM to lamina II inhibit mechanical nociceptive responses. There is strong evidence that these descending inhibitory mechanisms are suppressed in chronic pain states, which may contribute to various symptoms of chronic pain [1,20]. GlyT2 inhibitors could relieve many aspects of chronic pain by elevating synaptic glycine concentrations and thereby restoring glycinergic descending inhibition.…”

Section: Glycine Neurotransmission and Chronic Painmentioning

confidence: 99%