Aerobic Exercise Attenuates Pain Sensitivity: An Event-Related Potential Study

In this study, electroencephalography (EEG) was utilized to explore the neurophysiological mechanisms of aerobic exercise-induced hypoalgesia (EIH) and provide a theoretical basis for the application of aerobic exercise in pain assessment and treatment. Forty-five healthy subjects were randomly divided into moderate-intensity aerobic exercise [70% heart rate reserve (HRR)], low-intensity aerobic exercise (50% HRR), or control groups (sitting). Aerobic exercise was performed with cycling. Pressure pain threshold (PPT), heat pain threshold (HPT), event-related potential (ERP) induced by contact heat stimulus and pain scoring were measured before and after the intervention. We found that moderate-intensity aerobic exercise can increase the PPT (rectus femoris: t = −2.71, p = 0.017; tibialis anterior muscle: t = −2.36, p = 0.033) and HPT (tibialis anterior muscle: t = −2.219, p = 0.044) of proximal intervention sites rather than distal sites, and decreased pain scorings of contact heat stimulus. After moderate-intensity aerobic exercise, alpha oscillation power reflecting the central descending inhibitory function was enhanced (t = −2.31, p < 0.05). Low-intensity aerobic exercise mainly reduced the pain unpleasantness rating (Block 1: t = 2.415, p = 0.030; Block 2: t = 3.287, p = 0.005; Block 4: t = 2.646, p = 0.019; Block 5: t = 2.567, p = 0.022). Aerobic exercise had an overall EIH effect. Its hypoalgesic effect was related to exercise intensity and affected by the site and type of pain stimulus. Moderate-intensity aerobic exercise effectively reduced the sensitivity to various painful stimuli, and low-intensity aerobic exercise selectively inhibited the negative emotional pain response. The hypoalgesic mechanism of aerobic exercise involves the enhancement of the central descending inhibitory function.

Temporal properties of painful contrast enhancement using repetitive stimulation

Offset analgesia is characterized by a disproportionately large reduction in pain following a small decrease in a heat stimulus and is based on the phenomenon of temporal pain contrast enhancement (TPCE). The aim of this study is to investigate whether this phenomenon can also be induced by repetitive stimulation, i.e., by stimuli that are clearly separated in time. With this aim, the repetitive TPCE paradigm was induced in healthy, pain-free subjects (n=33) at the volar non-dominant forearm using heat stimuli. This paradigm was performed applying three different interstimulus intervals (ISIs): 5, 15, and 25 seconds. All paradigms were contrasted with a control paradigm without temperature change. Participants continuously rated the perceived pain intensity. In addition, electrodermal activity was recorded as a surrogate measure of autonomic arousal. Temporal pain contrast enhancement was confirmed for both ISI 5 seconds (p < 0.001) and ISI 15 seconds (p = 0.005), but not for ISI 25 seconds (p = 0.07), however the magnitude of TPCE did not differ between ISIs (p = 0.11). Electrodermal activity was consistent previous pain ratings, but showing significantly higher autonomic activity being measured. Thus, the phenomenon of temporal contrast enhancement of pain can also be induced by repetitive stimulation. Both the involvement of the autonomic nervous system and the involvement of habituation processes are conceivable, which consequently points to both central and peripheral mechanisms of TPCE.

Phase change mediated mechanically transformative dynamic gel for intelligent control of versatile devices

A phase change mediated mechanically transformative dynamic gel enables dramatic stiffness change under a heat stimulus for intelligent control of versatile devices.

The Perceived Opportunity to Avoid Pain Paradoxically Increases Pain-Related Fear Through Increased Threat Appraisals

Background Although pain-related avoidance is mainly intended to reduce the accompanying anticipatory fear, avoidance behavior may paradoxically increase fear when a previous avoidance response is no longer available, suggesting that there is a bidirectional relationship between pain-related fear and avoidance. Purpose We hypothesized that avoidance can serve as a source of information that fuels irrational pain-related threat appraisals, which, in turn, increases pain-related fear. Methods Participants (N = 66) were exposed to a painful heat stimulus and randomly assigned to the avoidance or control group. They were instructed to avoid the full heat intensity by pressing a stop button in the presence of a stop cue. Only avoidance group participants received a stop cue and were allowed to press the stop button, while control group participants received the same instructions but never had the opportunity to avoid the full heat intensity. In reality and unknown to participants, the intensity and duration of the heat stimulus was independent of the avoidance response. In the subsequent test phase, the avoidance response was unavailable for both groups. We measured pain-related fear, threat appraisals/harmfulness, and pain intensity. Results In line with our expectations, pain-related fear levels were higher when the avoidance response was no longer available compared to those when the avoidance response was available. Increased threat appraisals mediated the relationship between avoidance behavior and increased pain-related fear. Conclusions The perceived opportunity to avoid increased pain-related fear through threat appraisals, suggesting a more complicated relationship between pain-related fear, threat appraisals, and avoidance behavior than the unidirectional relationships proposed in the fear-avoidance model. Clinical implications are discussed.

Attenuation of IL-1ß on the use of glucosamine as an adjuvant in meloxicam treatment in rat models with osteoarthritis

BackgroundOsteoarthritis (OA) is the most prevalent joint disease and a common cause of joint pain, functional loss, and disability. The severity of this disease is always associated with increased levels of proinflammatory cytokines, which play an important role in cartilage damage, synovitis, and other damage to joint tissues. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an inflammatory state. Several studies show that cytokines, such as interleukin 1ß, have a major role in the development of inflammation that occurs in these joints. The use of glucosamine as an adjuvant to meloxicam therapy is expected to inhibit the development of inflammatory OA.MethodsThe OA model in rat was induced by single injection of intraarticular monosodium iodoacetate (MIA). The development of OA was observed for 21 days. Furthermore, the evaluation of glucosamine potency as an adjuvant of meloxicam therapy for reducing IL-1ß was done by combined treatment at a low dose of meloxicam 1 mg/kg BW with glucosamine at a dose of 125, 250, or 500 mg/kg BW orally for 28 days. Response to hyperalgesia and knee joint diameter was measured on days 0, 7, 14, 21, 28, 35, 42, and 49. IL-1ß levels were measured on day 21 and day 49 after MIA injection.ResultsMIA injection successfully induced OA as marked by a significant difference in the time of latency to heat stimulus (p < 0.01) and a significant increase in joint diameter (p < 0.01). On day 21, IL-1ß levels showed a significant decrease in MIA injection (p = 0.05). The administration of meloxicam and glucosamine did not induce significant decrease in knee joint diameter (p > 0.10), but was able to significantly increase the latency time to heat stimulus (p < 0.01). IL-1ß levels also showed a significant decrease after administering a combination of glucosamine and meloxicam (p < 0.01).ConclusionsTaken together, the use of glucosamine as an adjuvant in meloxicam therapy may be caused by the synergistic mechanism of meloxicam for the attenuation of OA development through systemically reducing IL-1ß.

Stepwise increasing sequential offsets cannot be used to deliver high thermal intensities with little or no perception of pain

Offset analgesia (OA) is the disproportionate decrease in pain experience following a slight decrease in noxious heat stimulus intensity. We tested whether sequential offsets would allow noxious temperatures to be reached with little or no perception of pain. Forty-eight participants continuously rated their pain experience during trials containing trains of heat stimuli delivered by Peltier thermode. Stimuli were adjusted through either stepwise sequential increases of 2°C and decreases of 1°C or direct step increases of 1°C up to a maximum of 46°C. Step durations (1, 2, 3, or 6 s) varied by trial. Pain ratings generally followed presented temperature, regardless of step condition or duration. For 6-s steps, OA was observed after each decrease, but the overall pain trajectory was unchanged. We found no evidence that sequential offsets could allow for little pain perception during noxious temperature presentation. NEW & NOTEWORTHY Offset analgesia is the disproportionate decrease in pain experience following a slight decrease in noxious heat stimulus intensity. We tested whether sequential offsets would allow noxious temperatures to be reached with little or no perception of pain. We found little evidence of such overall analgesia. In contrast, we observed analgesic effects after each offset with long-duration stimuli, even with relatively low-temperature noxious stimuli.

The Mechanistic Basis for Photobiomodulation Therapy of Neuropathic Pain by Near Infrared Laser Light

Background and Objective Various irradiances have been reported to be beneficial for the treatment of neuropathic pain with near infrared light. However, the mechanistic basis for the beneficial outcomes may vary based on the level of irradiance or fluence rate used. Using in vivo and in vitro experimental models, this study determined the mechanistic basis of photobiomodulation therapy (PBMT) for the treatment of neuropathic pain using a high irradiance.Study Design/Materials and Methods ln vitro experiments: Cultured, rat DRG were randomly assigned to control or laser treatment (L T) groups with different irradiation times (2, 5, 30, 60 or 120s). The laser parameters were: output power = 960 mW, irradiance = 300mW/cm2, 808 nm wavelength and spot size = 3cm diameter/ area = 7.07cm2, with different fluences according to irradiation times. Mitochondrial metabolic activity was measured with the MTS assay. The DRG neurons were immunostained using a primary antibody to β-Tubulin III. ln vivo experiments: spared nerve injury surgery (SNI), an animal model of persistent peripheral neuropathic pain, was used. The injured rats were randomly divided into three groups (n = 5). 1) Control: SNI without LT, 2) Short term: SNI with LT on day 7 and euthanized on day 7, 3) Long term: SNI with LT on day 7 and euthanized on day 22. An 808 nm wavelength laser was used for all treatment groups. Treatment was performed once on Day 7 post-surgery. The transcutaneous treatment parameters were: output power: 10 W, fluence rate: 270 mW/cm2, treatment time: 120s. The laser probe was moved along the course of the sciatic/sural nerve during the treatment. Within 1 hour of irradiation, behavior tests were performed to assess its immediate effect on sensory allodynia and hyperalgesia caused by SNI.Results ln vitro experiments: Mitochondrial metabolism was significantly lower compared with controls for all LT groups. Varicosities and undulations formed in neurites of DRG neurons with a cell body diameter 30µm or less. ln neurites of DRG neurons with a cell body diameter of greater than 30µm, varicosities formed only in the 120s group. ln vivo experiments: For heat hyperalgesia, there was a statistically significant reduction in sensitivity to the heat stimulus compared with the measurements done on day 7 prior to LT. A decrease in the sensitivity to the heat stimulus was found in the LT groups compared with the control group on day 15 and 21. For cold allodynia and mechanical hyperalgesia, a significant decrease in sensitivity to cold and pin prick was found within 1 hour after L T. Sensitivity to these stimuli returned to the control levels after 5 days post-L T. No significant difference was found in mechanical allodynia between control and L T groups for all time points examined.Conclusion These in vitro and in vivo studies indicate that treatment with an irradiance/fluence rate at 270 m W/cm2 or higher at the level of the nerve can rapidly block pain transmission. A combination therapy is proposed to treat neuropathic pain with initial high irradiance/fluence rates for fast pain relief, followed by low irradiance/fluence rates for prolonged pain relief by altering chronic inflammation.