Short-duration physical activity prevents the development of activity-induced hyperalgesia through opioid and serotoninergic mechanisms

Lucas V Lima; Josimari M DeSantana; Lynn A Rasmussen; Kathleen A Sluka

doi:10.1097/j.pain.0000000000000967

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Short-duration physical activity prevents the development of activity-induced hyperalgesia through opioid and serotoninergic mechanisms

Journal article

Peer reviewed

Short-duration physical activity prevents the development of activity-induced hyperalgesia through opioid and serotoninergic mechanisms

Lucas V Lima, Josimari M DeSantana, Lynn A Rasmussen and Kathleen A Sluka

Pain (Amsterdam), Vol.158(9), pp.1697-1710

09/2017

DOI: 10.1097/j.pain.0000000000000967

PMCID: PMC5561491

PMID: 28621702

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Abstract

Regular physical activity prevents the development of chronic muscle pain through the modulation of central mechanisms that involve rostral ventromedial medulla (RVM). We tested if pharmacological blockade or genetic deletion of mu-opioid receptors in physically active mice modulates excitatory and inhibitory systems in the RVM in an activity-induced hyperalgesia model. We examined response frequency to mechanical stimulation of the paw, muscle withdrawal thresholds, and expression of phosphorylation of the NR1 subunit of the N-methyl-D-aspartate receptor (p-NR1) and serotonin transporter (SERT) in the RVM. Mice that had performed 5 days of voluntary wheel running prior to the induction of the model were compared with sedentary mice. Sedentary mice showed significant increases in mechanical paw withdrawal frequency and a reduction in muscle withdrawal threshold; wheel running prevented the increase in paw withdrawal frequency. Naloxone-treated and MOR mice had increases in withdrawal frequency that were significantly greater than that in physically active control mice and similar to sedentary mice. Immunohistochemistry in the RVM showed increases in p-NR1 and SERT expression in sedentary mice 24 hours after the induction of the model. Wheel running prevented the increase in SERT, but not p-NR1. Physically active, naloxone-treated, and MOR mice showed significant increases in SERT immunoreactivity when compared with wild-type physically active control mice. Blockade of SERT in the RVM in sedentary mice reversed the activity-induced hyperalgesia of the paw and muscle. These results suggest that analgesia induced by 5 days of wheel running is mediated by mu-opioid receptors through the modulation of SERT, but not p-NR1, in RVM.

Pain Threshold - physiology

Receptors, Opioid, mu - metabolism

Mice, Inbred C57BL

Physical Conditioning, Animal - methods

Medulla Oblongata - metabolism

Receptors, N-Methyl-D-Aspartate - metabolism

Gene Expression Regulation - physiology

Hyperalgesia - prevention & control

Male

Mice, Knockout

Nerve Tissue Proteins - metabolism

Serotonin Plasma Membrane Transport Proteins - metabolism

Animals

Time Factors

Statistics, Nonparametric

Hyperalgesia - etiology

Female

Mice

Physical Stimulation - adverse effects

Receptors, Opioid, mu - genetics

Pain Measurement

Disease Models, Animal

Details

Title: Subtitle: Short-duration physical activity prevents the development of activity-induced hyperalgesia through opioid and serotoninergic mechanisms
Creators: Lucas V Lima - aDepartment of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, IA, USA bGraduate Program in Health Sciences, Federal University of Sergipe, Aracaju/Se, Brazil cDepartment of Physical Therapy, Federal University of Sergipe, Aracaju/Se, Brazil
Josimari M DeSantana
Lynn A Rasmussen
Kathleen A Sluka
Resource Type: Journal article
Publication Details: Pain (Amsterdam), Vol.158(9), pp.1697-1710
DOI: 10.1097/j.pain.0000000000000967
PMID: 28621702
PMCID: PMC5561491
NLM abbreviation: Pain
ISSN: 0304-3959
eISSN: 1872-6623
Publisher: United States
Grant note: R01 AR061371 / NIAMS NIH HHS
Language: English
Date published: 09/2017
Academic Unit: Iowa Neuroscience Institute; Nursing; Physical Therapy and Rehabilitation Science; Neuroscience and Pharmacology
Record Identifier: 9984040256602771

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