Reduction of conditioned pain modulation in humans by naltrexone: an exploratory study of the effects of pain catastrophizing

King, Christopher D.; Goodin, Burel R.; Kindler, Lindsay L.; Caudle, Robert M.; Edwards, Robert R.; Gravenstein, Nikolaus; Riley, Joseph L.; Fillingim, Roger B.

doi:10.1007/s10865-012-9424-2

Cited by 70 publications

(93 citation statements)

References 83 publications

(131 reference statements)

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“…51 However, the present findings indicate that additional opioid receptor blockade masked the analgesic response, thus supporting the view that opioid peptides play a primary role not only in the generalized form of conditioned pain modulation 18,30,32,35,38,54 but also in the lateralized type.…”

Section: Pain Ratings To Electrical Stimulation Of the Forearm Duringsupporting

confidence: 72%

“…We also investigated the effect of combined opioid receptor and α 2 -adrenoceptor blockade on pain ratings to electrical stimulation of the HFS-treated site in the forearm during and after painful stimulation of each temple. As opioid peptides contribute to conditioned pain modulation, 18,30,32,35,38,54 we hypothesized that opioid receptor blockade would inhibit the ipsilateral component of this response despite an opposing effect of yohimbine. 51…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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Involvement of Opioid Receptors and α2-Adrenoceptors in Inhibitory Pain Modulation Processes: A Double-Blind Placebo-Controlled Crossover Study

Hood

Drummond

2016

The Journal of Pain

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Accepted ManuscriptInvolvement of opioid receptors and α 2 -adrenoceptors in inhibitory pain modulation processes: a double-blind placebo-controlled crossover study This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 2 AbstractIn healthy humans, high-frequency electrical stimulation (HFS) of the forearm not only evokes local signs of central sensitization but also triggers broader ipsilateral inhibitory influences on pain akin to a lateralized form of conditioned pain modulation. Paradoxically, some of these inhibitory influences are augmented by α 2 -adrenoceptor blockade. To determine whether opioid peptides mediate inhibitory effects after HFS, the opioid receptor antagonist naltrexone was co-administered orally with the α 2 -adrenoceptor antagonist yohimbine in 16 healthy women in a double-blind placebo-controlled crossover study. In each session, mechanical sensitivity in the forearms and forehead was assessed before and after HFS. In addition, pain ratings to electrical stimulation of HFS-treated or control sites in the forearm were assessed during and after painful stimulation of each temple. Unlike yohimbine alone, the naltrexone + yohimbine combination blocked analgesia evoked by HFS in the ipsilateral forehead to blunt pressure, and opposed the ipsilateral inhibitory effect of pain in the temple on electrically-evoked pain at the HFS-treated site in the forearm. These findings imply involvement of opioid peptides in an ipsilateral analgesic response that complements the more generalized form of conditioned pain modulation. Opioid mediation of this ipsilateral analgesic response appears to override opposing α 2 -adrenoceptor effects.Perspective: HFS not only evokes local signs of central sensitization but also triggers a broader ipsilateral anti-nociceptive mechanism mediated by opioid receptors. Dysfunction of this lateralized pain modulation process might contribute to painful unilateral disorders such as migraine or complex regional pain syndrome.

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Section: Pain Ratings To Electrical Stimulation Of the Forearm Duringsupporting

confidence: 72%

Section: Accepted Manuscriptmentioning

confidence: 99%

Involvement of Opioid Receptors and α2-Adrenoceptors in Inhibitory Pain Modulation Processes: A Double-Blind Placebo-Controlled Crossover Study

Hood

Drummond

2016

The Journal of Pain

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“…Animal models and human studies suggest that the CPM is greatly dependent on the integrity of endogenous opioid (21) and descending bulbospinal serotonergic systems (6). Most recently, King and colleagues found that the administration of an opioid antagonist blocked the inhibition of focal heat pain of the palm during cold water immersion of the foot (21). Animal studies show that regular physical exercise increases endogenous opioid content in the central nervous system (e.g., cerebrospinal fluid and brainstem; 34) and the availability of serotonin in the brain (1).…”

Section: Discussionmentioning

confidence: 99%

Self-reported physical activity predicts pain inhibitory and facilitatory function

Naugle

Riley

2013

The Journal of Pain

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Considerable evidence suggests regular physical activity can reduce chronic pain symptoms. Dysfunction of endogenous facilitatory and inhibitory systems has been implicated in multiple chronic pain conditions. However, few studies have investigated the relationship between levels of physical activity and descending pain modulatory function.Purpose-This study's purpose was to determine whether self-reported levels of physical activity in healthy adults predicted 1) pain sensitivity to heat and cold stimuli, 2) pain facilitatory function as tested by temporal summation of pain (TS), and 3) pain inhibitory function as tested by conditioned pain modulation (CPM) and offset analgesia.Methods-Forty-eight healthy adults (age range 18-76) completed the International Physical Activity Questionnaire (IPAQ) and the following pain tests: heat pain thresholds (HPT), heat pain suprathresholds, cold pressor pain (CPP), temporal summation of heat pain, conditioned pain modulation, and offset analgesia. The IPAQ measured levels of walking, moderate, vigorous and total physical activity over the past seven days. Hierarchical linear regressions were conducted to determine the relationship between each pain test and self-reported levels of physical activity, while controlling for age, sex and psychological variables.Results-Self-reported total and vigorous physical activity predicted TS and CPM (p's <.05). Individuals who self-reported more vigorous and total physical activity exhibited reduced temporal summation of pain and greater CPM. The IPAQ measures did not predict any of the other pain measures.Conclusion-Thus, these results suggest that healthy older and younger adults who self-report greater levels of vigorous and total physical activity exhibit enhanced descending pain modulatory function. Improved descending pain modulation may be a mechanism through which exercise reduces or prevents chronic pain symptoms. KeywordsVigorous; Pain modulation; Temporal Summation; Conditioned Pain Modulation; ExerciseThe prevalence estimates of chronic pain among adults in the United States may be as high as 40%, affecting approximately 100 million adults (15). Pain increases physical disability (32), reduces quality of life, and is costly to both the individual experiencing pain and the Copyright © 2013 American College of Sports MedicineCorresponding Author: Kelly M. Naugle, College of Dentistry, University of Florida, 1329 SW 16 th Street, Rm 5180, Gainesville, FL 32608, Phone: 352-273-5975, Fax: 352-273-5985, knaugle@dental.ufl.edu. Conflict of InterestThere are not actual or potential conflicts of interest for any of the authors. The results of the present study do not constitute endorsement by ACSM. nation (15). Alarmingly, a recent study reported that the national cost of pain exceeds the cost of the nation's priority health conditions (e.g., cardiovascular disease, neoplasms, endocrine, nutritional and metabolic diseases), with costs ranging from $560 to $635 billion annually (15). Clearly, a need exists for effective meth...

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“…There are conflicting data on the effect of naloxone/naltrexone on CPM as some found inhibition of CMP (Pertovaara et al, 1982;Willer et al, 1990;King et al, 2013a) whereas others found no effect (Peters et al, 1992;Edwards et al, 2004;Sprenger et al, 2011).…”

Section: Targeting Descending Pathwaysmentioning

confidence: 99%

Assessment and manifestation of central sensitisation across different chronic pain conditions

Arendt-Nielsen

Morlion

Perrot

et al. 2017

European Journal of Pain

479

494

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Different neuroplastic processes can occur along the nociceptive pathways and may be important in the transition from acute to chronic pain and for diagnosis and development of optimal management strategies. The neuroplastic processes may result in gain (sensitisation) or loss (desensitisation) of function in relation to the incoming nociceptive signals. Such processes play important roles in chronic pain, and although the clinical manifestations differ across condition processes, they share some common mechanistic features. The fundamental understanding and quantitative assessment of particularly some of the central sensitisation mechanisms can be translated from preclinical studies into the clinic. The clinical perspectives are implementation of such novel information into diagnostics, mechanistic phenotyping, prevention, personalised treatment, and drug development. The aims of this paper are to introduce and discuss (1) some common fundamental central pain mechanisms, (2) how they may translate into the clinical signs and symptoms across different chronic pain conditions, (3) how to evaluate gain and loss of function using quantitative pain assessment tools, and (4) the implications for optimising prevention and management of pain. The chronic pain conditions selected for the paper are neuropathic pain in general, musculoskeletal pain (chronic low back pain and osteoarthritic pain in particular), and visceral pain (irritable bowel syndrome in particular). The translational mechanisms addressed are local and widespread sensitisation, central summation, and descending pain modulation. Significance Central sensitisation is an important manifestation involved in many different chronic pain conditions. Central sensitisation can be different to assess and evaluate as the manifestations vary from pain condition to pain condition. Understanding central sensitisation may promote better profiling and diagnosis of pain patients and development of new regimes for mechanism based therapy. Some of the mechanisms underlying central sensitisation can be translated from animals to humans providing new options in development of therapies and profiling drugs under development.

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Reduction of conditioned pain modulation in humans by naltrexone: an exploratory study of the effects of pain catastrophizing

Cited by 70 publications

References 83 publications

Involvement of Opioid Receptors and α2-Adrenoceptors in Inhibitory Pain Modulation Processes: A Double-Blind Placebo-Controlled Crossover Study

Involvement of Opioid Receptors and α2-Adrenoceptors in Inhibitory Pain Modulation Processes: A Double-Blind Placebo-Controlled Crossover Study

Self-reported physical activity predicts pain inhibitory and facilitatory function

Assessment and manifestation of central sensitisation across different chronic pain conditions

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