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Capturing the aversive state of cephalic pain preclinically.

ABSTRACT: Preclinical evaluation of headache by behavioral assessment of reward from pain relief.Inflammatory mediators (IMs) or control solution were applied to the rat dura mater to elicit a presumed state of cephalic pain. Hind paw incision was used in separate groups of animals to model noncephalic postsurgical pain. Drugs were given systemically or microinjected within the rostral ventromedial medulla (RVM), nucleus accumbens (NAc), or rostral anterior cingulate cortex (rACC). Peripheral nerve block was produced at the level of the popliteal fossa, and behavior was assessed using evoked sensory stimuli or conditioned place preference (CPP). Immunohistochemistry and brain microdialysis measurements were performed.Dural IMs produced long-lasting generalized cutaneous allodynia. RVM lidocaine produced CPP, increased NAc c-Fos, and dopamine release selectively in rats receiving dural IMs; CPP was blocked by intra-NAc ?-flupenthixol, a dopaminergic antagonist. Intravenous ?-calcitonin gene-related peptide (?CGRP)(8-37) produced CPP and elicited NAc dopamine release selectively in rats treated with dural IMs. Prior lesion of the rACC or treatment with systemic sumatriptan or ?CGRP(8-37) abolished RVM lidocaine-induced CPP in IM-treated rats. Sumatriptan treatment blocked NAc dopamine release in IM-treated rats receiving RVM lidocaine. Systemic sumatriptan did not alter pain relief-induced CPP in rats with incisional injury.Cephalic pain was unmasked in rats by assessment of motivated behavior to seek relief. Relief of pain activates the dopaminergic reward pathway to elicit negative reinforcement of behavior. Medications clinically effective for migraine headache selectively elicit relief of ongoing cephalic, but not postsurgical, noncephalic pain. These studies provide a platform for exploring migraine pathophysiology and for the discovery of new headache therapies.

SUBMITTER: De Felice M

PROVIDER: S-EPMC3830648 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Capturing the aversive state of cephalic pain preclinically.

De Felice Milena M Eyde Nathan N Dodick David D Dussor Gregory O GO Ossipov Michael H MH Fields Howard L HL Porreca Frank F

Annals of neurology 20130801 2

<h4>Objective</h4>Preclinical evaluation of headache by behavioral assessment of reward from pain relief.<h4>Methods</h4>Inflammatory mediators (IMs) or control solution were applied to the rat dura mater to elicit a presumed state of cephalic pain. Hind paw incision was used in separate groups of animals to model noncephalic postsurgical pain. Drugs were given systemically or microinjected within the rostral ventromedial medulla (RVM), nucleus accumbens (NAc), or rostral anterior cingulate cort ...[more]

PMID: 23686557

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Project description:BackgroundChronic pain is a common problem in adolescents that can negatively impact all aspects of their health-related quality of life. The developmental period of adolescence represents a critical window of opportunity to optimize and solidify positive health behaviors and minimize future pain-related disability and impaired work productivity. This research focuses on the development and evaluation of a smartphone-based pain self-management app for adolescents with chronic pain.ObjectiveThe objectives of this study were to characterize (1) the feasibility of deploying a mobile health (mHealth) app (iCanCope) to the personal smartphones of adolescent research participants; (2) adherence to daily symptom tracking over 55 consecutive days; (3) participant interaction with their symptom history; and (4) daily pain-related experiences of adolescents with chronic pain.MethodsWe recruited adolescents aged 15-18 years from 3 Canadian pediatric tertiary care chronic pain clinics. Participants received standardized instructions to download the iCanCope app and use it once a day for 55 days. Detailed app analytics were captured at the user level. Adherence was operationally defined as per the relative proportion of completed symptom reports. Linear mixed models were used to examine the trajectories of daily symptom reporting.ResultsWe recruited 60 participants between March 2017 and April 2018. The mean age of the participants was 16.4 (SD 0.9) years, and 88% (53/60) of them were female. The app was deployed to 98% (59/60) devices. Among the 59 participants, adherence was as follows: low (4, 7%), low-moderate (14, 24%), high-moderate (16, 27%), and high (25, 42%). Most (49/59, 83%) participants chose to view their historical symptom trends. Participants reported pain intensity and pain-related symptoms of moderate severity, and these ratings tended to be stable over time.ConclusionsThis study indicates that (1) the iCanCope app can be deployed to adolescents' personal smartphones with high feasibility; (2) adolescents demonstrated moderate-to-high adherence over 55 days; (3) most participants chose to view their symptom history; and (4) adolescents with chronic pain experience stable symptomology of moderate severity.Trial registrationClinicalTrials.gov NCT02601755; https://clinicaltrials.gov/ct2/show/NCT02601755 (Archived by WebCite at http://www.webcitation.org/74F4SLnmc).

Dataset Information

Capturing the aversive state of cephalic pain preclinically.

Publications

Capturing the aversive state of cephalic pain preclinically.

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