Analysis of Meaningful Conditioned Pain Modulation Effect in a Pain-Free Adult Population

Locke, David; Gibson, William; Moss, Penny; Munyard, Kylie; Mamotte, Cyril; Wright, Anthony

doi:10.1016/j.jpain.2014.09.001

Cited by 64 publications

(68 citation statements)

References 40 publications

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“…There is evidence that in a population of patients without pain, only 8% of individuals exhibit little or no CPM. 22 Multiple peripheral and September 2015 · Volume 156 · Number 9 www.painjournalonline.com 1809 central mechanisms will contribute to the variability of the pain experience for neuropathic pain patients, 35 and yet both a reduction 36 and a complete loss of DNIC (or CPM) are observed in patients with diabetic polyneuropathy. 24 In the SNL animals, DNIC was lost for the majority of neurons studied, both within the damaged nerve territory and contralaterally.…”

Section: Discussionmentioning

confidence: 99%

Diffuse noxious inhibitory controls and nerve injury

Bannister

Patel²,

Gonçalves³

et al. 2015

Pain

145

115

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Diffuse noxious inhibitory controls (DNICs) utilize descending inhibitory controls through poorly understood brain stem pathways. The human counterpart, conditioned pain modulation, is reduced in patients with neuropathy aligned with animal data showing a loss of descending inhibitory noradrenaline controls together with a gain of 5-HT3 receptor-mediated facilitations after neuropathy. We investigated the pharmacological basis of DNIC and whether it can be restored after neuropathy. Deep dorsal horn neurons were activated by von Frey filaments applied to the hind paw, and DNIC was induced by a pinch applied to the ear in isoflurane-anaesthetized animals. Spinal nerve ligation was the model of neuropathy. Diffuse noxious inhibitory control was present in control rats but abolished after neuropathy. α2 adrenoceptor mechanisms underlie DNIC because the antagonists, yohimbine and atipamezole, markedly attenuated this descending inhibition. We restored DNIC in spinal nerve ligated animals by blocking 5-HT3 descending facilitations with the antagonist ondansetron or by enhancing norepinephrine modulation through the use of reboxetine (a norepinephrine reuptake inhibitor, NRI) or tapentadol (μ-opioid receptor agonist and NRI). Additionally, ondansetron enhanced DNIC in normal animals. Diffuse noxious inhibitory controls are reduced after peripheral nerve injury illustrating the central impact of neuropathy, leading to an imbalance in descending excitations and inhibitions. Underlying noradrenergic mechanisms explain the relationship between conditioned pain modulation and the use of tapentadol and duloxetine (a serotonin, NRI) in patients. We suggest that pharmacological strategies through manipulation of the monoamine system could be used to enhance DNIC in patients by blocking descending facilitations with ondansetron or enhancing norepinephrine inhibitions, so possibly reducing chronic pain.

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Section: Discussionmentioning

confidence: 99%

Diffuse noxious inhibitory controls and nerve injury

Bannister

Patel²,

Gonçalves³

et al. 2015

Pain

145

115

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“…A second possible explanation for discrepancies in this literature stems from our observation that commonly-used mean pain ratings derived from multiple test stimuli administrations [19,30] could mask increases in CPM during the conditioning phase. Temporal changes in CPM during thermal pain have been previously reported for middle-age adults with chronic fatigue syndrome and healthy controls: whereas healthy controls exhibited CPM effects after a 15-second immersion in hot water (46 °C), patients with chronic fatigue syndrome only exhibited CPM effects after a 2-minute immersion [35].…”

Section: Discussionmentioning

confidence: 99%

Race Effects on Conditioned Pain Modulation in Youth

Morris¹,

Walker²,

Bruehl³

et al. 2015

The Journal of Pain

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Race and ethnicity shape the experience of pain in adults, with African Americans typically exhibiting greater pain intensity and evoked pain responsiveness than Non-Hispanic Whites. However, it remains unclear whether there are racial differences in conditioned pain modulation (CPM) and if these are present in youth. CPM refers to a reduction in perceived pain intensity for a test stimulus during application of a conditioning stimulus and may be especially relevant in determining risk for chronic pain. The present study assessed CPM to evoked thermal pain in 78 healthy youth (ages 10 to 17), 51% of whom were African American and 49% were Non-Hispanic White. African-American youth reported lower mean conditioning pain ratings than Non-Hispanic White youth, controlling for mean pre-conditioning pain ratings, which is consistent with stronger CPM. Multilevel models demonstrated stronger CPM effects in African-American than Non-Hispanic White youth, as evident in more rapid within-person decreases in pain ratings during the conditioning phase. These findings suggest that diminished CPM likely does not account for the enhanced responsiveness to evoked thermal pain observed in African-American youth. These results may have implications for understanding racial differences in chronic pain experience in adulthood. Perspective This study evaluated conditioned pain modulation to evoked thermal pain in African-American and Non-Hispanic White youth. Findings could have implications for the development of personalized chronic pain treatment strategies that are informed by race and ethnicity.

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“…Patients with chronic pain and deficits in CPM presented lower peripherally (plasma) acting norepinephrine and metanephrine concentrations (Parent et al, 2015). Lower CPM-mediated pain inhibition has also been linked to expression of a polymorphism in the serotonin transporter (5-HTT) gene (SLC6A4) (Lindstedt et al, 2011), but this association is not observed in all samples (Locke et al, 2014). …”

Section: A Few Other Pharmacological and Therapeutic Applicationsmentioning

confidence: 99%

Pain Modulation: From Conditioned Pain Modulation to Placebo and Nocebo Effects in Experimental and Clinical Pain

Damien

Colloca

Belleï-Rodriguez

et al. 2018

International Review of Neurobiology

105

107

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Accumulating evidence reveal important applications of endogenous pain modulation assessment in healthy controls and in patients in clinical settings, as dysregulations in the balance of pain modulatory circuits may facilitate pain and promote chronification of pain. This article reviews data on pain modulation, focusing on the mechanisms and translational aspects of pain modulation from conditioned pain modulation (CPM) to placebo and nocebo effects in experimental and clinical pain. The specific roles of expectations, learning, neural and neurophysiological mechanisms of the central nervous system are briefly reviewed herein. The interaction between CPM and placebo systems in pain inhibitory pathways is highly relevant in the clinic and in randomized controlled trials yet remains to be clarified. Examples of clinical implications of CPM and its relationship to placebo and nocebo effects are provided. A greater understanding of the role of pain modulation in various pain states can help characterize the manifestation and development of chronic pain and assist in predicting the response to pain-relieving treatments. Placebo and nocebo effects, intrinsic to every treatment, can be used to develop personalized therapeutic approaches that improve clinical outcomes while limiting unwanted effects.

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Analysis of Meaningful Conditioned Pain Modulation Effect in a Pain-Free Adult Population

Cited by 64 publications

References 40 publications

Diffuse noxious inhibitory controls and nerve injury

Diffuse noxious inhibitory controls and nerve injury

Race Effects on Conditioned Pain Modulation in Youth

Pain Modulation: From Conditioned Pain Modulation to Placebo and Nocebo Effects in Experimental and Clinical Pain

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