Immediate effects of transcutaneous electrical nerve stimulation (TENS) administered during resistance exercise on pain intensity and physical performance of healthy subjects: a randomized clinical trial.

PURPOSE: Exercise-induced muscle pain is a self-limiting condition which impacts physical activity habits. Transcutaneous electrical nerve stimulation (TENS) promotes pain reduction and functional improvement in different pain conditions. We propose that applying TENS during exercise might reduce pain and improve physical performance. Thus, we aimed to investigate immediate effects of TENS applied during resistance exercise. METHODS: Healthy subjects of both sexes, irregularly active or sedentary were assigned into two groups: active (n = 24) or placebo (n = 22) TENS. The study was conducted over five moments: on day 0, subjects were recruited, on day 1 subjects performed the one-repetition maximum test (1RM); 72 h later, on day 2, 1RM was retested; 48 h later, on day 3, TENS was applied during a functional-resisted exercise protocol for upper limbs (bench press and rowing), with an intensity of 80% of 1RM; and 24 h after, on day 4, subjects were reevaluated. Assessment included pain intensity at rest and with movement, pressure pain thresholds, and muscle fatigue. RESULTS: TENS did not reduce pain intensity when compared to placebo (p > 0.05). TENS reduce PPT in the latissmus dorsi: p = 0.02 and anterior tibialis: p = 0.04 in immediate reassessment. Immediate effects of TENS were significant for fatigue perception at rest (p = 0.01) and number of maximum repetitions during exercise sets, starting from the 5th set of rowing exercise (p = 0.002). CONCLUSION: Our results show that TENS did not reduce pain perception in healthy individuals, but its use induced increased muscle action, contributing to a greater fatigue perception.

Psychometric Analysis of Behavioral Pain Scale Brazilian Version in Sedated and Mechanically Ventilated Adult Patients: A Preliminary Study.

BACKGROUND AND PURPOSE: Pain assessment in Intensive Care Units (ICU) can be performed based on validated instruments as the Behavioral Pain Scale (BPS). Despite the existence of this clinical score, there is no Brazilian version of it to assess critically ill patients. This study aimed to translate the BPS into Brazilian Portuguese, verify its psychometric properties (reliability, validity, and responsiveness) and the correlation between pain measured and heart rate (HR), blood pressure (BP), Ramsay, and RASS scores. METHODS: Pain intensity by using Brazilian BPS version, HR, and BP were observed by 2 investigators during 3 different moments: at rest; during eye cleaning (EC); and tracheal suctioning (TS) in 15 adult subjects sedated and mechanically ventilated. Sedation level, severity of disease, and use of sedatives and analgesic drugs were also recorded. RESULTS: There was a high responsiveness coefficient (coefficient = 1.72) and pain was significantly higher during tracheal suctioning (P ≤ 0.003) and eye cleaning (P ≤ 0.04) than at rest. It was evidenced a low reliability and no significant correlation between translated BPS scores and physiological parameters during tracheal suctioning, sedation scales, flow of the sedatives drugs, or with the general health status (P > 0.07). CONCLUSION: Brazilian BPS has high responsiveness and capacity to detect pain intensity in different situations in the ICU routine. This preliminary study proved the feasibility and importance of valid this scale in Brazil in order to improve critically ill patients care.

Cyclodextrin-complexed Ocimum basilicum leaves essential oil increases Fos protein expression in the central nervous system and produce an antihyperalgesic effect in animal models for fibromyalgia.

O. basilicum leaves produce essential oils (LEO) rich in monoterpenes. The short half-life and water insolubility are limitations for LEO medical uses. ß-Cyclodextrin (ß-CD) has been employed to improve the pharmacological properties of LEO. We assessed the antihyperalgesic profile of LEO, isolated or complexed in ß-CD (LEO/ß-CD), on an animal model for fibromyalgia. Behavioral tests: mice were treated every day with either LEO/ß-CD (25, 50 or 100 mg/kg, p.o.), LEO (25 mg/kg, p.o.), tramadol (TRM 4 mg/kg, i.p.) or vehicle (saline), and 60 min after treatment behavioral parameters were assessed. Therefore, mice were evaluated for mechanical hyperalgesia (von Frey), motor coordination (Rota-rod) and muscle strength (Grip Strength Metter) in a mice fibromyalgia model. After 27 days, we evaluated the central nervous system (CNS) pathways involved in the effect induced by experimental drugs through immunofluorescence protocol to Fos protein. The differential scanning analysis (DSC), thermogravimetry/derivate thermogravimetry (TG/DTG) and infrared absorption spectroscopy (FTIR) curves indicated that the products prepared were able to incorporate the LEO efficiently. Oral treatment with LEO or LEO-ßCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia and we were able to significantly increase Fos protein expression. Together, our results provide evidence that LEO, isolated or complexed with ß-CD, produces analgesic effects on chronic non-inflammatory pain as fibromyalgia.

A systematic review of the wound-healing effects of monoterpenes and iridoid derivatives.

The search for more effective and lower cost therapeutic approaches for wound healing remains a challenge for modern medicine. In the search for new therapeutic options, plants and their metabolites are a great source of novel biomolecules. Among their constituents, the monoterpenes represent 90% of essential oils, and have a variety of structures with several activities such as antimicrobial, anti-inflammatory, antioxidant and wound healing. Based on that, and also due to the lack of reviews concerning the wound-healing activity of monoterpenes, we performed this systematic review-which provides an overview of their characteristics and mechanisms of action. In this search, the terms "terpenes", "monoterpenes", "wound healing" and "wound closure techniques" were used to retrieve articles published in LILACS, PUBMED and EMBASE until May 2013. Seven papers were found concerning the potential wound healing effect of five compouds (three monoterpenes and two iridoid derivatives) in preclinical studies. Among the products used for wound care, the films were the most studied pharmaceutical form. Monoterpenes are a class of compounds of great diversity of biological activities and therapeutic potential. The data reviewed here suggest that monoterpenes, although poorly studied in this context, are promising compounds for the treatment of chronic wound conditions.

Immediate post-craniotomy headache.

INTRODUCTION: Headache is the most common adverse event immediately following craniotomy and is due to the surgical procedure and meningeal irritation. OBJECTIVES: The aim of this study was to investigate the prevalence of headache during the first week after a craniotomy, as well as headache intensity, whether pain was registered in the patient's medical records, the use of analgesics and predictors of headache. METHODS: Ninety-one patients who underwent craniotomy were evaluated from the first to the seventh post-operative day. The variables analysed were gender, age, medical history, indication for craniotomy, surgery, occurrence of headache, pain registration in the medical records, length of hospital stay and analgesics consumption. RESULTS: On the second post-operative day, 29.2% of patients had a headache and there was under-reporting of this pain in the patients' records. The analgesics used were non-steroidal anti-inflammatory in 75% of cases. An age of <45 years (odds ratio = 3.0, P = 0.041) and surgery duration lasting >4 hours (odds ratio = 3.7, P = 0.019) were associated with the occurrence of immediate post-craniotomy headache. CONCLUSION: Further training should be provided to professionals caring for patients undergoing craniotomy to better manage post-operative headache.

Effect of Transcutaneous Electrical Nerve Stimulation on Pain-related Quantitative Sensory Tests in Chronic Musculoskeletal Pain and Acute Experimental Pain: Systematic Review and Meta-analysis.

This report provides a systematic review of the literature to analyze the effects of transcutaneous electrical nerve stimulation (TENS) on analgesia on sensitization measures, in studies with chronic musculoskeletal pain and in studies with acute experimental pain. The protocol was registered at PROSPERO (CRD42020213473). The authors searched Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature via Biblioteca Virtual de Saúde, Physiotherapy Evidence Database, PubMed, ScienceDirect, Web of Science, Google Scholar, and hand-searched reference lists were also conducted. Among 22,252 manuscripts found, 58 studies were included in the systematic review and 35 in the meta-analysis. Thirty-four studies assessed pain intensity; 24 studies investigated hyperalgesia; temporal summation was only evaluated in 2 studies; and conditioned pain modulation was not observed in the included studies. Meta-analyses favored TENS, despite its limitations and heterogeneity. Primary hyperalgesia in studies with musculoskeletal pain presented a high level of evidence, while other outcomes presented moderate evidence in the studies that were included. It is not possible to infer results about both temporal summation and conditioned pain modulation. Moderate evidence suggests that TENS promotes analgesia by reducing both central and peripheral sensitization, as shown by the reduction in primary and secondary hyperalgesia, pain intensity at rest, and during movement in experimental acute pain and chronic musculoskeletal pain. Overall, both types of studies analyzed in this review presented meta-analyses favorable to the use of TENS (compared to placebo TENS), showing reductions in both primary and secondary hyperalgesia, as well as decreases in pain intensity at rest and in motion. PERSPECTIVE: This article presents data from the literature on the effect of TENS through sensitization assessments in individuals with chronic musculoskeletal pain, or acute experimental pain. These data contribute to knowledge about pain neuroscience research, using TENS technology.

Bioassay-guided evaluation of antinociceptive effect of N-salicyloyltryptamine: a behavioral and electrophysiological approach.

We investigated the antinociceptive and nerve excitability effects of the N-salicyloyltryptamine (NST) NST-treated mice exhibited a significant decrease in the number of writhes when 100 and 200 mg/kg (i.p.) were administered (i.p.). This effect was not antagonized by naloxone (1.5 mg/kg, i.p.). NST inhibited the licking response of the injected paw when 100 and 200 mg/kg were administered (i.p.) to mice in the first and second phases of the formalin test. Because the antinociceptive effects could be associated with neuronal excitability inhibition, we performed the single sucrose gap technique and showed that NST (3.57 mM) significantly reduced (29.2%) amplitude of the compound action potential (CAP) suggesting a sodium channel effect induced by NST. Our results demonstrated an antinociceptive activity of the NST that could be, at least in part, associated to the reduction of the action potential amplitude. NST might represent an important tool for pain management.

Antinociceptive activity of atranorin in mice orofacial nociception tests.

Physicochemical characterization and antinociceptive and anti-inflammatory activities of atranorin (AT) extracted from Cladina kalbii Ahti in formalin- and capsaicin-induced orofacial pain and anti-inflammatory tests in rodents were studied. Physicochemical characterization showed that AT has the general formula C19H18O8. Male Swiss mice were pretreated with AT (100, 200, and 400 mg/kg, i.p.), morphine (3 mg/kg, i.p.), or vehicle (0.9% saline with two drops of 0.2% Tween 80) before formalin (20 microl, 2%) or capsaicin (20 microl, 2.5 microg) were injected into the right vibrissa. Our results showed that i.p. treatment with AT displayed marked inhibitory effects in different orofacial pain tests in mice. AT (400 mg/kg, i.p.) was effective in reducing the nociceptive face-rubbing behavioural response in both phases of the formalin test, which was also naloxone-sensitive. Additionally, AT produced a significant antinociceptive effect at all doses in the capsaicin test. Such results were unlikely to be provoked by motor abnormality, since AT-treated mice exhibited no performance alteration on the rota rod apparatus. AT exhibited significant anti-inflammatory activity in the acute model of inflammation (leukocyte migration to the peritoneal cavity), carrageenan- and arachidonic acid-induced hind paw edema in rats. Additionally, AT exhibited a dose-dependent antioxidant activity in vitro, as assessed by total radical-trapping antioxidant parameter and total antioxidant reactivity assays. All these findings suggest that AT might represent an important tool for the management of orofacial pain and/or inflammatory disorders.

Effect of dance on lower-limb range of motion in young people with cerebral palsy: a blinded randomized controlled clinical trial.

PURPOSE: One of the most limiting conditions in cerebral palsy (CP) is the impairment in musculoskeletal mobility. CP may impair the ability to perform efficient movements. The aim of this trial was to investigate the effect of dance on the range of motion (ROM) of lower limbs in young people with CP. PATIENTS AND METHODS: the randomized clinical trial consisted of two groups: dance group (DG) and control group (CG). Both of them underwent a 1-hour treatment, twice a week, for 2 months. Sanny® pendulum fleximeter was used to measure ROM in pre- and posttreatment. The applied procedures in both groups were conducted at suitable locations. Twenty-six participants were allocated to these two groups of study. RESULTS: In DG, the sampling variances showed improvements in all lower limb joints and axes of movements (P<0.05). In CG, there was increase in passive ROM in some lower limb joints (P≤0.05). CONCLUSION: Physical intervention is imperative to improve ROM. It seems dance practice can contribute to CP corporal mobility in a positive way. CLINICAL TRIAL NUMBER: Nº CAAE-06154012.4.0000.0058-12, number 98.993.

Comparison between functional and traditional training exercises on joint mobility, determinants of walking and muscle strength in older women.

BACKGROUND: Currently, several strength training protocols have been verified aiming improvements on functionality in older population. For this purpose, integrated exercises aimed at improving essential movements may be an interesting strategy in improving performance for daily activities. This randomized trial compared the effects of eight and twelve weeks of functional and traditional training (TT) on joint mobility, gait determinants and muscle strength, and verified the maintenance of the effects after eight weeks of detraining in the older women. METHODS: Fifty-two older women were randomized into three groups: Functional Training (FT: N.=19), TT (TT: N.=16) and Stretching Group (SG: N.=17). The data were analyzed by ANOVA with Bonferroni post-hoc test. RESULTS: The FT and TT groups obtained significant improvements in the tests of muscle strength and muscle power both after twelve weeks of intervention, as well as with SG. Only the FT presented statistically significant improvements in dynamic agility/balance (32%, P=0.000), and cardiorespiratory condition (8.71%, P=0.020) in relation to SG. CONCLUSIONS: The experimental protocols are equally effective in improving joint mobility and strength components in active older women. However, FT seems to be more effective than TT in the improvement of the determinants of gait ability.

Reliability of a Test for Assessment of Isometric Trunk Muscle Strength in Elderly Women.

OBJECTIVE: The aim of this study was to analyze the reproducibility of a protocol using the maximal isometric strength test of the trunk in elderly women aged above 60 years, without low back pain. METHODS: Twenty-one physically inactive elderly women, who had not engaged in any activity or exercise program in the past three months, participated in the cross-sectional study that consisted of two days of evaluations for the maximal isometric strength of the extensor and flexor muscles of the trunk, with a 48 h interval between the sessions. A platform with fixed seating was used, which allowed the fixation of the hip and lower limbs, with a load cell connected to a linear encoder. To verify the reliability of the test, the interclass correlation coefficient, variation coefficient, minimum detectable difference (MDD), standard error of measurement, and Bland-Altman graphs were calculated. RESULTS: No statistical difference was observed between the first and second evaluation, which indicates that there was no learning effect. Interclass correlation coefficient values were classified as very high and high for extensor (0.98) and flexor (0.86) muscles, respectively, besides low variation (9% for both muscle groups) and acceptable values for minimum detectable difference (extensors = 51.1 N, flexors = 48.9 N). In addition, the Bland-Altman analysis revealed low bias and values within the limits of agreement. CONCLUSION: It is concluded that the test of maximum isometric strength of the trunk in healthy and trained elderly people presents high reliability. These values proved to be reliable if performed in at least two evaluation sessions, which confirms the hypothesis of the authors by the consistency of the measurement test.

Effectiveness of transcutaneous electrical nerve stimulation for treatment of hyperalgesia and pain.

Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacologic treatment for pain relief. TENS has been used to treat a variety of painful conditions. This review updates the basic and clinical science regarding the use of TENS that has been published in the past 3 years (ie, 2005-2008). Basic science studies using animal models of inflammation show changes in the peripheral nervous system, as well as in the spinal cord and descending inhibitory pathways, in response to TENS. Translational studies show mechanisms to prevent analgesic tolerance to repeated application of TENS. This review also highlights data from recent randomized, placebo-controlled trials and current systematic reviews. Clinical trials suggest that adequate dosing, particularly intensity, is critical to obtaining pain relief with TENS. Thus, evidence continues to emerge from both basic science and clinical trials supporting the use of TENS for the treatment of a variety of painful conditions while identifying strategies to increase TENS effectiveness.

Modulation between high- and low-frequency transcutaneous electric nerve stimulation delays the development of analgesic tolerance in arthritic rats.

OBJECTIVE: To investigate whether repeated administration of modulating frequency transcutaneous electric nerve stimulation (TENS) prevents development of analgesic tolerance. DESIGN: Knee joint inflammation (3% carrageenan and kaolin) was induced in rats. Either mixed or alternating frequency was administered daily (20min) for 2 weeks to the inflamed knee under light halothane anesthesia (1%-2%). SETTING: Laboratory. ANIMALS: Adult male Sprague-Dawley rats (N=36). INTERVENTION: Mixed- (4Hz and 100Hz) or alternating- (4Hz on 1 day; 100Hz on the next day) frequency TENS at sensory intensity and 100micros pulse duration. MAIN OUTCOME MEASURES: Paw and joint withdrawal thresholds to mechanical stimuli were assessed before induction of inflammation, and before and after daily application of TENS. RESULTS: The reduced paw and joint withdrawal thresholds that occur 24 hours after the induction of inflammation were significantly reversed by the first administration of TENS when compared with sham treatment or to the condition before TENS treatment, which was observed through day 9. By the tenth day, repeated daily administration of either mixed- or alternating-frequency TENS did not reverse the decreased paw and joint withdrawal thresholds. CONCLUSIONS: These data suggest that repeated administration of modulating frequency TENS leads to a development of opioid tolerance. However, this tolerance effect is delayed by approximately 5 days compared with administration of low- or high-frequency TENS independently. Clinically, we can infer that a treatment schedule of repeated daily TENS administration will result in a tolerance effect. Moreover, modulating low and high frequency TENS seems to produce a better analgesic effect and tolerance is slower to develop.

Central mechanisms in the maintenance of chronic widespread noninflammatory muscle pain.

Chronic widespread pain (CWP) conditions such as fibromyalgia and myofascial syndromes are characterized by generalized pain, tenderness, morning stiffness, disturbed sleep, and pronounced fatigue. However, CWP pathophysiology is still unclear. A number of hypotheses have been proposed as the underlying pathophysiology of CWP: muscular dysfunction/ischemia, central sensitization, and a deficit in endogenous pain-modulating systems. This article reviews the current and emerging literature about the pathophysiology and neurobiology of chronic widespread -musculoskeletal pain. Widespread musculoskeletal pain results in changes in the central nervous system in human subjects and animal models. These changes likely reflect alterations in supraspinal modulation of nociception, and include increases in excitatory and decreases in inhibitory modulation pathways. These alterations in excitation and inhibition likely drive changes observed in the spinal cord to result in central sensitization, and the consequent pain and hyperalgesia.

Correlations between brain changes and pain management after cognitive and meditative therapies: A systematic review of neuroimaging studies.

BACKGROUND: There are different ways of dealing with pain and cognitive and meditative therapies (CMT) are alternative ways to regulate the emotions associated with pain. Current studies apply neuroimaging techniques trying to elucidate the neural mechanisms of cognitive strategies for pain. This systematic review aimed to summarize the evidence on brain activity changes after CMT, which include cognitive behavioral therapy, mindfulness and/or meditation, for pain management as well as to evaluate clinical pain outcomes. METHODS: Electronic databases - Pubmed, EMBASE, PsycINFO, Science Direct, Scopus - were searched to find randomized controlled trials (RCTs) examining neuroimaging data of CMT for chronic pain patients or healthy individuals with experimental pain. Two reviewers independently selected the relevant trials, rated for quality assessment and extracted all data using a standardized form. Primary outcome was brain activity changes (activation, deactivation or functional connectivity). Secondary outcomes were pain intensity, self-management, pain coping, quality of life, anxiety and depression. RESULTS: Nine RCTs were included involving 280 adults (18-59 years), 139 chronic pain patients vs. 148 healthy subjects. Three main kinds of intervention were identified: cognitive-behavioral therapy (n = 4), mindfulness meditation (n = 4) and transcendental meditation technique (n = 1). Neuroimaging results revealed distinct patterns of activity, but the main findings were related to increased activation of prefrontal cortex (PFC), specially dorsolateral prefrontal cortex (dlPFC) and ventrolateral prefrontal cortex (vlPFC), orbitofrontal cortex (OBF), somatosensory cortices (SSC) and limbic system in chronic pain population; and increased activation of anterior cingulate cortex (ACC), anterior insular cortex (AI) and decreased activation of thalamus in healthy individuals following CMT. CONCLUSION: This result means that regulation of pain by CMT can alter functioning of brain regions in an extensive network including non-nociceptive regions. CMT reduced the affective experience of pain, while reductions of pain intensity ratings were less consistent. Brain changes have been demonstrated as a result of the application of psychological measures and may represent the clinical implications of changes in brain activity or morphology.

Does Electroacupuncture Treatment Reduce Pain and Change Quantitative Sensory Testing Responses in Patients with Chronic Nonspecific Low Back Pain? A Randomized Controlled Clinical Trial.

Chronic nonspecific low back pain is common and one of the most disabling conditions in the world. There is moderate evidence that chronic low back pain patients present altered functional connectivity in areas related to pain processing. Quantitative sensory testing is a way of clinical measure of these alterations. Although there is not enough evidence, there are some reports that electroacupuncture is supposedly more effective in relieving pain than acupuncture because the addition of electric current could optimize the effects of traditional technique. Thus, the objective of this randomized clinical trial was to verify if electroacupuncture treatment reduces pain and changes quantitative sensory testing responses in patients with chronic nonspecific low back pain. Patients were evaluated before and after 10 sessions regarding pain (11-point numerical rating pain scale) and quantitative sensory testing (pressure pain threshold, temporal summation, and conditioned pain modulation). There were 1 treatment group (electroacupuncture (EA)) and three different control groups (CTR 1, CTR 2, and CTR 3). A total of 69 patients participated in the study. No significant differences were found in pain intensity or quantitative sensory testing responses when comparing electroacupuncture group to the three control groups. There was a significant reduction in both resting and movement pain intensity in groups EA, CTR 1, and CTR3. Although ten sessions of electroacupuncture have diminished pain intensity in both resting and movement, it could not change significantly quantitative sensory testing and diminish central sensitization in patients with chronic nonspecific low back pain. The implications of this study involve the fact that, maybe, in chronic nonspecific low back pain, electroacupuncture should be associated with other treatments that target central sensitization.

The inclusion complex of carvacrol and ß-cyclodextrin reduces acute skeletal muscle inflammation and nociception in rats.

BACKGROUND: Skeletal muscle inflammation is strongly associated with pain and may impair regeneration and functional recovery after injury. Since anti-inflammatory and antinociceptive effects have been described for the inclusion complex of carvacrol and ß-cyclodextrin (ßCD-carvacrol), this study investigated the effects of ßCD-carvacrol in a model of acute skeletal muscle inflammation. METHODS: Muscle injury was induced in male Wistar rats by injection of 3% carrageenan in the gastrocnemius muscle. Rats were orally pretreated with saline (vehicle) or ßCD-carvacrol (20, 40, 80 and 180 mg/kg) one hour before administration of carrageenan. RESULTS: The injection of carrageenan in the gastrocnemius muscle increased tissue myeloperoxidase (MPO) activity (p < 0.001), edema (p < 0.001) and the levels of tumoral necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, macrophage inflammatory protein (MIP-2), but not IL-10 levels. Also, it increased mechanical hyperalgesia and decreased the grip force of animals. Pretreatment with ßCD-carvacrol (80 or 160 mg/kg) significantly decreased muscle MPO activity and edema 24 h after injury in comparison to vehicle-pretreated group. Animals pretreated with ßCD-carvacrol (160 mg/kg) presented significantly lower levels of IL-1ß, IL-6 and MIP-2 and higher levels of IL-10 six hours after induction and lower levels of TNF-α and MIP-2 after 24 h when compared to the vehicle group. Pretreatment with ßCD-carvacrol also reduced mechanical hyperalgesia and limited the decrease of grip force (80 or 160 mg/kg; p < 0.001) 6 and 24 h after injury. CONCLUSION: These results show that ßCD-carvacrol reduces inflammation and nociception in a model of acute injury to skeletal muscles.

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

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.

Does electrode placement influence tens-induced antihyperalgesia in experimental inflammatory pain model?

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is a treatment commonly used for managing pain; however, the ideal placement of the electrodes is not fully understood. OBJECTIVE: To investigate the best way to apply TENS electrodes in an experimental inflammatory pain model. METHOD: Knee joint inflammation was induced in rats, followed by administration of low-frequency TENS (4Hz) under anesthesia for five days. Animals were randomly allocated to five groups according to electrode placement (n=6, each): dermatome, contralateral, paraspinal, acupoint, and control. INTERVENTIONS: Low-frequency TENS at sensory intensity and 100µs pulse duration. Withdrawal thresholds to mechanical (von Frey) and thermal stimuli and joint edema were assessed before induction of inflammation and immediately before and after application of TENS. RESULTS: Reduced paw withdrawal threshold and thermal latency that occur 24h after the induction of inflammation were significantly reversed by the administration of TENS in all groups when compared with sham treatment or with the condition before TENS treatment. No difference was observed in the edema measurement. CONCLUSION: These results offer more options for practitioners to choose the area of the body most commodious for electrode placement, depending on the clinical condition of the patient, because the effect was similar at all sites. In addition, there was a loss of the effectiveness of TENS in reversing mechanical and thermal hyperalgesia on the fifth day, suggesting the development of the tolerance phenomenon.