Endorphin mediated increase in pain threshold induced by long-lasting exercise in rats

doi:10.1016/0024-3205(82)90597-5

Life Sciences

Volume 30, Issue 10, 8 March 1982, Pages 833-840

https://doi.org/10.1016/0024-3205(82)90597-5 Get rights and content

Abstract

Rats were trained to run spontaneously, without stress, in running wheels. The running activity increased gradually and could reach a plateau of 7 km/night after 3–4 weeks. During the first hour of running in the dark phase the squeak threshold increased significantly and remained high in the morning. The degree of increased threshold was correlated to the amount of running activity. The squeak threshold declined during the following 6 hours of inactivity. A rapid decrease in threshold occurred after naloxone (1–2 mg/kg i.p.). It is suggested that long-lasting muscle exercise (e.g. jogging), acupuncture, and low frequency electrical stimulation of afferent nerve fibres produce discharges in muscle afferents which influence central endorphin mechanics giving analgetic effects.

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Cited by (101)

Hyperlocomotor activity and stress vulnerability during adulthood induced by social isolation after early weaning are prevented by voluntary running exercise before normal weaning period
2014, Behavioural Brain Research
Citation Excerpt :
In addition, the EI + R rats were allowed access to the running wheel immediately before the behavioral tests during the juvenile period. Since running exercise acutely affects a variety of physiological systems, including autonomic nervous activities, endocrine activities, pain sensitivity [65–67], and monoamine neurotransmission, the acute effects of running exercise may also be the reason for the increased stress vulnerability in juvenile EI + R rats. The EI rats did not show an increase in LH after exposure to SI during the juvenile period, but adult period.
In rodents, the disruption of social-rearing conditions before normal weaning induces emotional behavioral abnormalities, such as anxiety, motor activity dysregulation, and stress vulnerability. The beneficial effects of exercise after normal weaning on emotional regulation have been well documented. However, effects of exercise before normal weaning on emotion have not been reported. We examined whether voluntary wheel running (R) during social isolation after early weaning (early weaning/isolation; EI) from postnatal day (PD) 14–30 could prevent EI-induced emotional behavioral abnormalities in Sprague–Dawley rats. Compared with control rats reared with their dam and siblings until PD30, rats performed R during EI (EI + R) and EI rats demonstrated greater locomotion and lower grooming activity in the open-field test (OFT) during the juvenile period. Juvenile EI ± R rats showed greater learned helplessness (LH) after exposure to inescapable stress (IS; electric foot shock) than IS-exposed control and EI rats. In contrast, EI rats showed increased locomotion in the OFT and LH after exposure to IS compared with control rats during adulthood; this was not observed in EI ± R rats. Both EI and EI ± R rats exhibited greater rearing activity in the OFT than controls during adulthood. EI did not increase anxiety in the OFT and elevated plus-maze. These results suggested that R during EI until normal weaning prevented some of the EI-induced behavioral abnormalities, including hyperlocomotor activity and greater LH, during adulthood but not in the juvenile period.
Similarities between exercise-induced hypoalgesia and conditioned pain modulation in humans
2014, Pain
Citation Excerpt :
Experimental studies have examined the effect of acute exercise, and the majority have documented a multisegmental decrease in pain sensitivity during and following exercise in healthy subjects [30]. Aerobic exercise (eg, bicycling or running) produces a hypoalgesic effect when performed at moderate to high intensities for longer periods [15,18,40]. In contrast, isometric exercise (ie, a muscle contraction without joint movement) produces EIH at both low and high intensity and duration seems to be of less importance [13,46].
Pain inhibitory mechanisms are often assessed by paradigms of exercise-induced hypoalgesia (EIH) and conditioned pain modulation (CPM). In this study it was hypothesized that the spatial and temporal manifestations of EIH and CPM were comparable. The participants were 80 healthy subjects (40 females), between 18 and 65 years of age in this randomized, repeated-measures cross-over trial that involved data collection on 2 different days. CPM was assessed by 2 different cold pressor tests (hand and foot). EIH was assessed by 2 intensities of aerobic bicycling exercises and 2 intensities of isometric muscle contraction exercises (arm and leg). Pressure pain thresholds (PPTs) were recorded before, during, after, and 15 minutes after conditioning/exercise at sites local to and remote from the extremity used for cold pressor stimulation and exercise. PPTs increased at local as well as at remote sites during both cold pressor tests and after all of the exercise conditions except low-intensity bicycling. EIH after bicycling was higher in women than in men. CPM and the EIH responses after isometric exercises were comparable in men and women and were not affected by age. The EIH response was larger in the exercising body part compared with nonexercising body parts for all exercise conditions. High-intensity exercise produced greater EIH responses than did low-intensity exercise. The change in PPTs during cold pressor tests and the change in PPTs after exercises were not correlated. The CPM response was not dominated by local manifestations, and the effect was seen only during the stimulation, whereas exercise had larger local manifestations, and the effects were also found after exercise.
Changes in pain perception and hormones pre- and post-kumdo competition
2013, Hormones and Behavior
Citation Excerpt :
However, a human exercise study demonstrated that plasma levels of beta-endorphin immunoreactive material (IRM) increase two- to five-fold after submaximal exercise (Farrell et al., 1982). It has also been shown that the administration of an opioid receptor antagonist, naloxone, decreased the analgesic effects induced by exercise (Haier et al., 1981; Paulev et al., 1989; Shyu et al., 1982). These studies suggest that in the future, a study using opioid antagonists is needed to evaluate whether beta-endorphins could contribute to analgesic effects pre- and post-competition.
The psychological stress of competition is a powerful stimulus affecting numerous hormones, which in turn change how pain is perceived. This study investigated whether a kumdo (kendo) team competition may be related to changes in hormones and pain. Seventeen healthy male kumdo practitioners participated in this experiment. Pain experiments were conducted by applying noxious stimuli with a thermal stimulator 10 min before a kumdo competition and 30 min post-competition. Serum testosterone, cortisol, beta-endorphin levels, pain thresholds, pain ratings at 48 °C and during blood sampling (sampling pain), anxiety, blood pressure, and heart rate were measured pre- and post-competition. Anxiety, pain threshold, testosterone/cortisol ratio, and blood pressure were significantly higher pre-competition compared to post-competition, while cortisol and pain ratings were significantly lower pre-competition than post-competition. There were significant correlations between the number of previous competitions and testosterone levels both pre-competition and post-competition. In pre-competition measurements, sampling pain increased with an increase in systolic blood pressure, heart rate, and beta-endorphins, and a decrease in age. In post-competition measurements, sampling pain increased with an increase in diastolic blood pressure and a decrease in testosterone levels. These results indicate that severe psychological pre-competition stress was associated with reduced pain ratings, perhaps in order to improve athletic performance. This also suggests that competitors may be at risk of potential injury due to changes in pain perception, and careful consideration should be taken to avoid potential injury before and during competition.
An fMRI study on the acute effects of exercise on pain processing in trained athletes
2012, Pain
Citation Excerpt :
Also, the raised incidence of silent myocardial ischemia in athletes [52] may be explained by raised opioidergic tone, thereby blunting the alerting pain symptoms of ischemia. Pain threshold elevations induced by regular exercise are reversed by the opioid receptor antagonist naloxone [53] and the antinociceptive effects of exogenous opiates are attenuated by exercise, a phenomenon referred to as cross-tolerance [36]. Similar cross-tolerance effects can also be elicited directly by local morphine administration into the periaqueductal gray (PAG) [37], a key area of the descending antinociceptive pathway that receives input from the pregenual anterior cingulate cortex (pgACC) to mediate opioidergic antinociceptive effects [45].
Endurance exercise is known to promote sustained antinociceptive effects, and there is evidence that the reduction of pain perception mediated by exercise is driven by central opioidergic neurotransmission. To directly investigate the involved brain areas and the underlying neural mechanisms in humans, thermal heat-pain challenges were applied to 20 athletes during 4 separate functional magnetic resonance imaging (fMRI) scans, i.e., before and after 2 hours of running (exercise condition) and walking (control condition), respectively. Imaging revealed a reproducible pattern of distributed pain-related activation in all 4 conditions, including the mesial and lateral pain systems, and the periaqueductal gray (PAG) as a key region of the descending antinociceptive pathway. At the behavioral level, running as compared with walking decreased affective pain ratings. The influence of exercise on pain-related activation was reflected in a significant time × treatment interaction in the PAG, along with similar trends in the pregenual anterior cingulate cortex and the middle insular cortex, where pain-induced activation levels were elevated after walking, but decreased or unchanged after running. Our findings indicate that enhanced reactive recruitment of endogenous antinociceptive mechanisms after aversive repeated pain exposure is attenuated by exercise. The fact that running, but not walking, reproducibly elevated β-endorphin levels in plasma indicates involvement of the opioidergic system in exercise. This may argue for an elevated opioidergic tone in the brain of athletes, mediating antinociceptive mechanisms. Our findings provide the first evidence using functional imaging to support the role of endurance exercise in pain modulation.
Involvement of the nitric oxide/<inf>C</inf>GMP/K<inf>ATP</inf> pathway in antinociception induced by exercise in rats
2010, Life Sciences
Physical exercise is responsible for increasing the nociceptive threshold. The present study aimed to investigate the involvement of the nitric oxide/_CGMP/K_ATP pathway in antinociception induced by acute aerobic exercise (AAc) in rats.
Wistar rats performed exercise in a rodent treadmill, according to an AAc protocol. The nociceptive threshold was measured by mechanical and thermal nociceptive tests (paw-withdrawal, tail-flick and face-flick). To investigate the involvement of the NO/_CGMP/K_ATP pathway the following nitric oxide synthase (NOS) unspecific and specific inhibitors were used: N-nitro-l-arginine (NOArg), Aminoguanidine, N⁵-(1-Iminoethyl)-l-ornithine dihydrocloride (L-NIO), N^ω-Propyl-l-arginine (L-NPA); guanylyl cyclase inhibitor, 1H-[1,2,4]oxidiazolo[4,3-a]quinoxalin-1-one (ODQ); and K_ATP channel blocker, Glybenclamide; all administered subcutaneously at a dose of 2 mg/kg 10 min before exercise started. Plasma and cerebrospinal fluid (CSF) nitrite levels were determined by spectrophotometry.
In the paw-withdrawal, tail-flick and face-flick tests, the AAc protocol produced antinociception, which lasted for more than 15 min. This effect was significantly reversed (P < 0.05) by NOS specific and unspecific inhibitors, guanylyl cyclase inhibitor (ODQ) and K_ATP channel blocker (Glybenclamide). Acute exercise was also responsible for increasing nitrite levels in both plasma and cerebrospinal fluid.
Taken together, these results suggest that the NO/_CGMP/K_ATP pathway participates in antinociception induced by exercise.
Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model: Role of endogenous opioids
2011, Anesthesiology
Exercise is often prescribed as a therapy for chronic pain. Short-term exercise briefly increases the production of endogenous analgesics, leading to transient antinociception. In limited studies, exercise produced sustained increases in endogenous opioids, sustained analgesia, or diminished measures of chronic pain. This study tests the hypothesis that regular aerobic exercise leads to sustained reversal of neuropathic pain by activating endogenous opioid-mediated pain modulatory systems.
After baseline measurements, the L5 and L6 spinal nerves of male Sprague–Dawley rats were tightly ligated. Animals were randomized to sedentary or 5-week treadmill exercise–trained groups. Thermal and tactile sensitivities were assessed 23 h after exercise, using paw withdrawal thresholds to von Frey filaments and withdrawal latencies to noxious heat. Opioid receptor antagonists were administered by subcutaneous, intrathecal, or intracerebroventricular injection. Opioid peptides were quantified using immunohistochemistry with densitometry.
Exercise training ameliorated thermal and tactile hypersensitivity in spinal nerve–ligated animals within 3 weeks. Sensory hypersensitivity returned 5 days after discontinuation of exercise training. The effects of exercise were reversed by using systemically or intracerebroventricularly administered opioid receptor antagonists and prevented by continuous infusion of naltrexone. Exercise increased β-endorphin and met-enkephalin content in the rostral ventromedial medulla and the mid-brain periaqueductal gray area.
Regular moderate aerobic exercise reversed signs of neuropathic pain and increased endogenous opioid content in brainstem regions important in pain modulation. Exercise effects were reversed by opioid receptor antagonists. These results suggest that exercise-induced reversal of neuropathic pain results from an up-regulation of endogenous opioids.

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Endorphin mediated increase in pain threshold induced by long-lasting exercise in rats

Abstract

Endeavour

Life Sci.

Brain Res.

Brain Res.

Lancet

Lancet

Pain

Life Sci.

Brain Res.

Exp. Neurol.

Life Sci.

Scientia Sinica