Experimental Muscle Pain Research Articles

Psychophysical changes after total sleep deprivation and experimental muscle pain.

Sleep disturbances exacerbate chronic pain, increase psychological load, and increase inflammation. Delayed onset muscle soreness (DOMS) mimics aspects of chronic pain, predominantly affecting peripheral pain mechanisms, while experimental sleep provocations have been shown to impact central pain mechanisms. This study aimed to combine a DOMS model with total sleep deprivation (TSD) to create a novel model affecting both peripheral and central pain mechanisms. A total of 30 healthy participants attended two sessions (baseline and follow-up) separated by 24 h of TSD and a home rating after 48 h. Assessments of interleukin 6 (IL-6) levels, sleep quality, pain catastrophising, affect, and symptoms of depression and anxiety were included in the baseline and follow-up sessions. Additionally, pressure pain and tolerance thresholds, temporal summation, and conditioned pain modulation (CPM) were assessed using cuff-pressure algometry in the baseline and follow-up sessions. DOMS was induced with eccentric calf raises during the baseline session followed by 24 h of TSD. At follow-up pain tolerance (p = 0.012) was significantly reduced, and CPM (p = 0.036) was significantly impaired compared to baseline. Psychological changes included decreases in pain catastrophising (p = 0.027), positive affect (p < 0.001), negative affect (p = 0.003), and anxiety (p = 0.012). Explorative regression models predicted 58% and 68% of DOMS pain intensity after 24 and 48 h, respectively, based on baseline body mass index, pain thresholds, psychological measures, and IL-6 (p < 0.01). Combining DOMS with 1 night of TSD induced pain hypersensitivity, impaired CPM, and altered psychological states. A combination of baseline inflammation, psychological measures, and pain sensitivity significantly predicted DOMS pain intensity after 24 and 48 h.

Experimentally induced pain increases absolute but not relative errors and reduces variability in joint repositioning of the knee joint in healthy participants

BackgroundJoint position sense (JPS) plays an important role in knee joint function. Despite the possible influence of pain on the proprioceptive system, the effects of experimental muscle pain on knee JPS have not been studied. ObjectivesTo investigate if experimentally induced muscle pain affects knee JPS in healthy participants. MethodsMeasurements of knee JPS were conducted before and after the injection of 5.8% sterile hypertonic saline in the vastus medialis muscle of 26 healthy physically active adults. Knee JPS was assessed through a passive/active repositioning paradigm in target angles of 15°, 45° and 60° using an isokinetic dynamometer. Absolute and relative angular errors were calculated. The coefficient of variation analysis was used to assess differences in the angles’ variability during the repositioning task. ResultsAbsolute angular error increased in all three angles following experimentally induced pain. The difference was statistically significant at 45° (p = 0.003, d = 0.6) and 15° (p = 0.047, d = 0.4) but not at 60° (p = 0.064, d = 0.4). Relative error did not show directional bias at 45° (p = 0.272, d = 0.2), 15° (p = 0.483, d = 0.1) or 60° (p = 0.091, d = 0.3). The coefficient of variation analysis revealed a statistically significant reduction in variability at angles of 60° (p = 0.002, d = 0.7) and 15° (p = 0.031, d = 0.4) after the pain intervention. ConclusionThe presence of experimentally induced muscle pain affects the ability of healthy participants to accurately reposition the knee at two angles of knee flexion and reduces movement variability during the repositioning task. Further research is required to determine if these deficits also impact patients with clinical knee pain.

Spatiotemporal characterization of an experimental model of muscle pain in humans based on short-wave diathermy.

Commonly used models for eliciting muscle pain involve the injection of algesic substances or the induction of delayed onset muscle soreness. The former require invasive procedures, and the time frame for pain induction and subsidence in the latter can be inconvenient. This study presents a detailed spatiotemporal characterization of a new experimental model of muscle pain based on short-wave diathermy (SWD), developed to overcome the limitations of existing models. The shoulder was selected as target site and the effects of the model were tested in two sessions to assess its reliability. Pain intensity profiles were recorded during the application of SWD, and changes in pressure pain threshold (PPT) in the infraspinatus muscle, together with pain intensity, duration, and quality were assessed 30 min after induction. SWD-induced pain intensity scores averaged 4 points on a visual analogue scale, whereas PPT showed a consistent decrease of about 25% relative to baseline values. Pain was localized in the shoulder area, and was described as continuous, dull, well-delimited, heavy, and bearable. Pain lasted for an average of 145 min without requiring reinduction and was reliably elicited in both experimental sessions. SWD can be used to elicit experimental muscle pain in a non-invasive, long-lasting, and reliable way and allows for repeated within- and between-session testing in the shoulder. SWD produces deep heating in muscles by converting electromagnetic energy to thermal energy. It was previously shown that it can be used to elicit experimental pain in the forearm muscles, and the present study demonstrates that this can be reliably generalized to other body sites, such as the shoulder. Furthermore, SWD application is non-invasive and presents a convenient time frame for pain induction and subsidence, thus overcoming limitations associated with traditional muscle pain models.

Impact of streptozotocin-induced diabetes on experimental masseter pain in rats.

This study aimed to assess the influence of streptozotocin (STZ)-induced diabetes on the nociceptive behavior evoked by the injection of hypertonic saline (HS) into the masseter muscle of rats. Forty male rats were equally divided into four groups: a) isotonic saline control, which received 0.9% isotonic saline (IS), (Ctrl-IS); b) hypertonic saline control, which received 5% HS (Ctrl-HS); c) STZ-induced diabetic, which received IS, (STZ-IS); d) STZ-induced diabetic, which received HS (STZ-HS). Experimental diabetes was induced by a single intraperitoneal injection of STZ at dose of 60 mg/kg dissolved in 0.1 M citrate buffer, and 100 μL of HS or IS were injected into the left masseter to measure the nociceptive behavior. Later on, muscle RNA was extracted to measure the relative expression of the following cytokines: cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and interleukins (IL)-1β, -2, -6, and -10. One-way analysis of variance (ANOVA) was applied to the data (p < 0.050). We observed a main effect of group on the nociceptive response (ANOVA: F = 11.60, p < 0.001), where the Ctrl-HS group presented the highest response (p < 0.001). However, nociceptive response was similar among the Ctrl-IS, STZ-IS, and STZ-HS group (p > 0.050). In addition, the highest relative gene expression of TNF-α and IL-6 was found in the masseter of control rats following experimental muscle pain (p < 0.050). In conclusion, the loss of somatosensory function can be observed in deep orofacial tissues of STZ-induced diabetic rats.

Intra- and interindividual reliability of muscle pain induced by an intramuscular injection of hypertonic saline injection into the quadriceps.

Intramuscular injections of hypertonic saline are commonly used to induce experimental muscle pain, but reliability data on this technique are lacking. This study investigated the intra- and interindividual reliability of pain measures from a hypertonic saline injection into the vastus lateralis. Fourteen healthy participants (6 female) attended three laboratory visits where they received an intramuscular injection of 1 mL hypertonic saline into the vastus lateralis. Changes in pain intensity were recorded on an electronic visual analogue scale, and pain quality was assessed after pain had resolved. Reliability was assessed with the coefficient of variation (CV), minimum detectable change (MDC) and intraclass correlation coefficient (ICC) with 95% CIs. Mean pain intensity displayed high levels of intraindividual variability (CV = 16.3 [10.5-22.0]%) and 'poor' to 'very good' relative reliability (ICC = 0.71 [0.45-0.88]) but had a MDC of 11 [8-16] au (out of 100). Peak pain intensity exhibited high levels of intraindividual variability (CV = 14.8 [8.8-20.8]%) with 'moderate' to 'excellent' levels of relative reliability (ICC = 0.81 [0.62-0.92]), whereas the MDC was 18 [14-26] au. Measures of pain quality exhibited good reliability. Interindividual variability in pain measures was high (CV > 37%). Intramuscular injections of 1 mL of hypertonic saline into the vastus lateralis display substantial levels of interindividual variability, but MDC is below the clinically important changes in pain. This model of experimental pain is suitable for studies involving repeated exposures. Many pain research studies have performed intramuscular injections of hypertonic saline to investigate responses to muscle pain. However, the reliability of this technique is not well established. We examined the pain response over three repeated sessions of a hypertonic saline injection. The pain induced by hypertonic saline has considerable interindividual variability but has largely acceptable intraindividual reliability. Therefore, the injections of hypertonic saline to induce muscle pain are a reliable model of experimental muscle pain.

Effects of conditioned pain modulation on Capsaicin-induced spreading muscle hyperalgesia in humans.

Muscle pain can be associated with hyperalgesia that may spread outside the area of primary injury due to both peripheral and central sensitization. However, the influence of endogenous pain inhibition is yet unknown. This study investigated how endogenous pain inhibition might influence spreading hyperalgesia in experimental muscle pain. Conditioned pain modulation (CPM) was assessed in 30 male volunteers by cold pressor test at the non-dominant hand as conditioning and pressure pain thresholds (PPT) at the dominant 2nd toe as test stimuli. Subjects were classified as having inhibitory or facilitating CPM based on published reference values. Subsequently, muscle pain and hyperalgesia were induced by capsaicin injection into the non-dominant supraspinatus muscle. Before and 5, 10, 15, 20, 30, 40, 50 and 60 min later, PPTs were recorded at the supraspinatus, infraspinatus and deltoid muscle, ring finger and toe. Compared to baseline, PPTs decreased at the supraspinatus, infraspinatus and deltoid muscle (p≤0.03), and increased at the finger and toe (p<0.001). In facilitating CPM (n=10), hyperalgesia occurred at 5, 10, 15, 20 and 40 min (p≤0.026). In inhibitory CPM (n=20), hyperalgesia only occurred after 10 and 15 min (p≤0.03). At the infraspinatus muscle, groups differed after 5 and 40 min (p≤0.008). The results suggest that facilitating CPM is associated with more spreading hyperalgesia than inhibitory CPM. This implies that poor endogenous pain modulation may predispose to muscle pain and spreading hyperalgesia after injury, and suggest that strategies to enhance endogenous pain modulation may provide clinical benefits.

Extensive Sensorimotor Training Predetermines Central Pain Changes During the Development of Prolonged Muscle Pain

Repetitive movements (RM) are a main risk factor for musculoskeletal pain, which is partly explained by the overloading of musculoskeletal structures. However, RM may also drive brain plasticity, leading to maladaptive changes in sensorimotor areas and altered pain processing. This study aimed to understand whether individuals performing extensive RM (musicians) exhibit altered brain processing to prolonged experimental muscle pain. Nineteen healthy musicians and 20 healthy nontrained controls attended 3 sessions (Day 1–Day 3–Day 8). In each session, event-related potentials (ERPs) to non-nociceptive superficial and nociceptive intraepidermal electrical stimulation, reaction times, electrical detection thresholds, and pressure pain thresholds (PPTs) were recorded. In all participants, prolonged muscle pain was induced by intramuscular injection of nerve growth factor (NGF) into the right first dorsal interosseous muscle at the end of Day1. Pain intensity was assessed on a numerical rating scale (NRS) and was lower in musicians compared to non-musicians (P < .007). Moreover, in musicians, the higher amount of weekly training was associated with lower NRS pain scores on Day 3 to Day 8 (P < .037). Compared with Day1, NGF reduced PPTs on Day 3 to Day 8 (P < .001) and non-nociceptive P200 and P300 ERP amplitudes on Day 8 (P < .044) in both groups. Musicians compared to controls showed secondary hyperalgesia to electrical stimulation on Day 3 to Day 8 (P < .004) and reduced nociceptive P200 ERP amplitudes on Day 8 (P < .005). Across participants, ERP components correlated with pain detection reaction times, sensitivity (PPTs and electrical detection thresholds), and severity (NRS), (all P < .043). These results show that repetitive sensorimotor training leads to brain changes in the processing of prolonged pain, biasing the cortical response to nociceptive inputs. PerspectiveRepetitive sensorimotor training may increase the responsiveness of nociceptive inputs during the development of prolonged muscle pain. These novel data highlight the role of repetitive sensorimotor practice as a source for interindividual variability in central pain processing.

The temporal expression of circulating microRNAs after acute experimental pain in humans.

MicroRNAs (miRNAs) can modulate several biological systems, including the pain system. This study aimed to evaluate the temporal expression of circulating miRNAs in the plasma of healthy volunteers as a marker for epigenetic changes before and after an acute, experimental, pain provocation by intramuscular hypertonic saline injection. Twenty volunteers were randomly allocated into two groups and received either hypertonic (pain) or isotonic (control) saline injection in the first dorsal interosseous muscle of their dominant hand. Pain intensity was continuously recorded for 20minutes after injection on a VAS scale from 0 to 100 (0 indicates no pain and 100 the worst imaginable pain). Blood samples were taken at baseline, 30minutes, 3hours, and 24hours post-injection, and plasma was separated. MiRNA extracts were used for RNA sequencing with the Illumina NextSeq platform. MiRNA transcripts were compared between the pain and the no-pain, control group at every time point. Significant differences were considered when folds were >2 and the False Discovery Rate was p< 0.05. After 30minutes, 4 miRNAs were significantly altered in the pain group compared to controls, which increased to 24 after 3 hours and to 42 after 24hours from baseline (p< 0.0001). Two miRNAs were consistently upregulated throughout the experiment. Enrichment analysis showed significant miRNAs involved in brain perception of pain, brain signalling and response to stimuli. This exploratory study is the first to report on the temporal expression of circulating miRNAs after an acute, human experimental muscle pain model. This exploratory study evaluated the temporal profile of circulating miRNAs in the plasma of healthy subjects after acute experimental pain. Several miRNAs were altered in subjects at the times of follow-up after the acute pain model when compared to controls. MiRNAs previously associated with pain processes were altered in the pain group. Our results, by showing the fast and prolonged modifications of miRNA elicited by the acute experimental pain model, add new perspectives to the topic of epigenetics and pain.

Non-uniform Effects of Nociceptive Stimulation to Motoneurones during Experimental Muscle Pain

Nociceptive stimulation is predicted to uniformly inhibit motoneurone pools of painful muscles and those producing painful movements. Although reduced motoneurone discharge rate during pain provides some evidence, recent data show evidence of increased excitability of some motoneurones. These observations suggest non-uniform effects of nociception on motoneurone excitability. More direct measures are required, but this is difficult to assess as few measures enable in vivo evaluation of motoneurone excitability in humans. We investigated changes in motoneurone excitability during experimental pain using two methods in separate experiments: (i) estimation of the time-course of motoneurone afterhyperpolarization (AHP) from interval death rate analysis of interspike intervals of single motor unit discharge; and (ii) probability of early motoneurone discharge to a descending volley excited using transcranial magnetic stimulation (TMS). Tibialis anterior motor units were recorded with fine-wire electrodes before, during and after painful infusion of 5% hypertonic saline into the muscle. Activation of 17 units (16 participants) could be used for AHP analysis. Data show shortened (n = 11) and lengthened (n = 6) AHP time-course. Increased (n = 6) and decreased (n = 6) probability of early motoneurone discharge were observed in the TMS experiment. These convergent observations suggest non-uniform effects of nociceptive stimulation on motoneurone pools. This does not support the hypothesis that nociceptive input induces uniform inhibition of painful muscle. Instead, interpretation of results implies redistribution of activity between motor units, with possible benefit for unloading painful tissues. This finding supports an interpretation that differs from the generally accepted view in pain physiology regarding adaptation to motor function in pain.

Acute experimentally-induced pain replicates the distribution but not the quality or behaviour of clinical appendicular musculoskeletal pain. A systematic review

Abstract Objectives Experimental pain is a commonly used method to draw conclusions about the motor response to clinical musculoskeletal pain. A systematic review was performed to determine if current models of acute experimental pain validly replicate the clinical experience of appendicular musculoskeletal pain with respect to the distribution and quality of pain and the pain response to provocation testing. Methods A structured search of Medline, Scopus and Embase databases was conducted from database inception to August 2020 using the following key terms: “experimental muscle pain” OR “experimental pain” OR “pain induced” OR “induced pain” OR “muscle hyperalgesia“ OR (“Pain model” AND “muscle”). Studies in English were included if investigators induced experimental musculoskeletal pain into a limb (including the sacroiliac joint) in humans, and if they measured and reported the distribution of pain, quality of pain or response to a provocation manoeuvre performed passively or actively. Studies were excluded if they involved prolonged or delayed experimental pain, if temporomandibular, orofacial, lumbar, thoracic or cervical spine pain were investigated, if a full text of the study was not available or if they were systematic reviews. Two investigators independently screened each title and abstract and each full text paper to determine inclusion in the review. Disagreements were resolved by consensus with a third investigator. Results Data from 57 experimental pain studies were included in this review. Forty-six of these studies reported pain distribution, 41 reported pain quality and six detailed the pain response to provocation testing. Hypertonic saline injection was the most common mechanism used to induce pain with 43 studies employing this method. The next most common methods were capsaicin injection (5 studies) and electrical stimulation, injection of acidic solution and ischaemia with three studies each. The distribution of experimental pain was similar to the area of pain reported in clinical appendicular musculoskeletal conditions. The quality of appendicular musculoskeletal pain was not replicated with the affective component of the McGill Pain Questionnaire consistently lower than that typically reported by musculoskeletal pain patients. The response to provocation testing was rarely investigated following experimental pain induction. Based on the limited available data, the increase in pain experienced in clinical populations during provocative maneuvers was not consistently replicated. Conclusions Current acute experimental pain models replicate the distribution but not the quality of chronic clinical appendicular musculoskeletal pain. Limited evidence also indicates that experimentally induced acute pain does not consistently increase with tests known to provoke pain in patients with appendicular musculoskeletal pain. The results of this review question the validity of conclusions drawn from acute experimental pain studies regarding changes in muscle behaviour in response to pain in the clinical setting.

Experimental muscle pain and music, do they interact?

Music is used to evoke audio analgesia during dental procedures, but it is unknown if experimental pain and music interact. This study aimed to explore the multisensory interaction between contrasting types of music and experimentally induced muscle pain. In 20 healthy women, 0.3mL sterile hypertonic saline (5.8%) was injected into the masseter muscle during three sessions while contrasting music (classical and black metal) or no music was played in the background. Pain intensity was assessed every 15seconds with a 0-100mm visual analogue scale (VAS) until pain subsided. Pain spread (pain drawings), unpleasantness (VAS), anxiety (VAS), and pain quality (McGill Questionnaire) were assessed after the last pain assessment. Pain of high intensity was evoked at all sessions with a median (interquartile range) peak pain intensity of 78 (30) in the black metal music, 86 (39) in the classical music, and 77 (30) in the control session. The pain duration was 142 (150) seconds in the black metal music, 135 (150) seconds in the classical music, and 135 (172) seconds in the control session. The corresponding pain-drawing areas were 42 (52), 37 (36), and 44 (34), arbitrary units respectively. There were no differences in any of these variables (Friedman's test; P´s>.368), or in unpleasantness, anxiety, or pain quality between sessions (P´s>.095). Experimentally induced muscle pain does not seem to be influenced by contrasting types of background music. Further studies exploring the multisensory integration between music and experimental muscle pain are needed.

Fear of movement is associated with corticomotor depression in response to acute experimental muscle pain.

Acute musculoskeletal pain is associated with reductions in corticomotor output that persists even after pain resolves. Factors that contribute to corticomotor depression following acute pain are unknown. This study examined whether psychological factors, including pain catastrophising, kinesiophobia, and implicit theories of pain, were associated with corticomotor depression following acute experimental muscle pain. Forty-two healthy individuals participated. Participants completed three questionnaires: Pain Catastrophising Scale, Tampa Scale of Kinesiophobia, and Implicit Theories of Pain Scale. Acute pain was induced into the right extensor carpi radialis brevis (ECRB) muscle by injection of hypertonic saline. Corticomotor depression was assessed as a reduction in motor-evoked potentials measured from ECRB muscle in response to transcranial magnetic stimulation before, immediately after, and at 10, 20, and 30min following pain resolution. Corticomotor depression was present at each time point relative to baseline (p < 0.001). Higher levels of kinesiophobia were associated with less corticomotor depression 10-min post pain resolution (r = 0.32, p = 0.03), but not at any other time point (p > 0.11). When corticomotor depression was compared between individuals with 'high' and 'low' kinesiophobia, a similar relationship was observed: Individuals with high compared to low kinesiophobia displayed less corticomotor depression immediately after (p = 0.02) and 10min post pain (p = 0.02), but not at 20 or 30min (p = 0.05 for both). No relationship was observed with any other psychological variable (p > 0.15). These data provide preliminary support for a relationship between pain-related fear of movement and corticomotor depression in response to acute pain. These findings may have implications for clinical musculoskeletal pain disorders.

Low-threshold motor units can be a pain during experimental muscle pain.

Low-threshold motor units can be a pain during experimental muscle pain.

Divergent response of low- versus high-threshold motor units to experimental muscle pain.

The neural strategies behind the control of force during muscle pain are not well understood as previous research has been limited in assessing pain responses only during low-force contractions. Here we compared, for the first time, the behaviour of motor units recruited at low and high forces in response to pain. The results showed that motor units activated at low forces were inhibited while those recruited at higher forces increased their activity in response to pain. When analysing lower- and higher-threshold motor unit behaviour at high forces we observed differential changes in discharge rate and recruitment threshold across the motor unit pool. These adjustments allow the exertion of high forces in acutely painful conditions but could eventually lead to greater fatigue and stress of the muscle tissue. During low-force contractions, motor unit discharge rates decrease when muscle pain is induced by injecting nociceptive substances into the muscle. Despite this consistent observation, it is currently unknown how the central nervous system regulates motor unit behaviour in the presence of muscle pain at high forces. For this reason, we analysed the tibialis anterior motor unit behaviour at low and high forces. Surface EMG signals were recorded from 15 healthy participants (mean age (SD) 26 (3) years, six females) using a 64-electrode grid while performing isometric ankle dorsiflexion contractions at 20% and 70% of the maximum voluntary force (MVC). Signals were decomposed and the same motor units were tracked across painful (intramuscular hypertonic saline injection) and non-painful (baseline, isotonic saline, post-pain) contractions. At 20% MVC, discharge rates decreased significantly in the painful condition (baseline vs. pain: 12.7 (1.1) Hz to 11.5 (0.9) Hz, P<0.001). Conversely, at 70% MVC, discharge rates increased significantly during pain (baseline vs. pain: 19.7 (2.8) Hz to 21.3 (3.5) Hz, p=0.029) and recruitment thresholds decreased (baseline vs. pain: 59.0 (3.9)%MVC to 55.9 (3.2)%MVC, p=0.02). These results show that there is a differential adjustment between low- and high-threshold motor units during painful conditions. An increase in excitatory drive to high-threshold motor units is likely required to compensate for the inhibitory influence of nociceptive afferent inputs on low-threshold motor units. These differential mechanisms allow the force output to be maintained during acute pain but this strategy could lead to increased muscle fatigue and symptom aggravation in the long term.

The Effect of Granisetron on Sensory Detection and Pain Thresholds in Facial Skin of Healthy Young Males.

Background: The specific serotonin type 3 (5-HT3)-receptor antagonist granisetron effectively reduces clinical as well as experimental muscle pain and hyperalgesia and with a duration that exceeds that of lidocaine. Hence, it may be an alternative to lidocaine as a local anesthetic. There are also some indications that granisetron in addition to 5-HT3 receptors blocks sodium channels. Thus, the local anesthetic effect by granisetron may resemble that of lidocaine, but this has not been tested. The aim of this study was therefore to compare the effect granisetron has on facial skin sensitivity to the effect of lidocaine and isotonic saline.Methods: This was a randomized, controlled, and double-blind study, in which 1 ml of either granisetron (test-substance), lidocaine (positive control), or isotonic saline (negative control) was injected into the skin over the masseter muscle at three different occasions in 18 healthy males (27.2 ± 5.8 years old). Skin detection thresholds and pain thresholds for thermal stimuli as well as mechanical detection thresholds and sensitivity to a painful mechanical (pinprick) stimulus were assessed before (baseline) and 5, 20, 40, and 60 min after injection. The quality and area of subjective sensory change over the cheek were assessed 20 min after injection.Results: All substances increased the mechanical detection threshold (granisetron: p = 0.011; lidocaine: p = 0.016; saline: p = 0.031). Both granisetron and lidocaine, but not isotonic saline, increased the heat detection thresholds (p < 0.001 and p < 0.02, respectively), but not the cold detection thresholds. Granisetron and lidocaine also reduced pinprick pain (p = 0.001 for each comparison). There were no significant differences between granisetron and lidocaine for any of these variables. There was no effect on thermal pain thresholds for any substance.Conclusion: The similar analgesic patterns on mechanical sensory and pain thresholds as well as thermal sensory thresholds over the facial skin by subcutaneous injection of granisetron and lidocaine shown in this study and the absence of paresthesia, in combination with the reduced pain intensity and pressure pain sensitivity shown in previous studies, indicate that granisetron might be a novel candidate as a local anesthetic.

Repeated buffered acidic saline infusion in the human masseter muscle as a putative experimental pain model

This study investigated if repeated buffered acidic saline infusions into the masseter muscles induced muscle pain and mechanical sensitization. Fourteen healthy men participated in this double-blind, randomized, and placebo-controlled study. Two repeated infusions (day 1 and 3) were given in the masseter muscles with either a buffered acidic saline solution (pH 5.2) or an isotonic saline solution (pH 6) as control. After 10 days of wash-out, the experiment was repeated with the other substance. Pressure pain thresholds (PPT), pain intensity, maximum unassisted mouth opening (MUO), and pain drawings were assessed before, directly following, and after each infusion at 5, 15, and 30 min and on day 4 and 7. Fatigue and pain intensity were assessed after a one-minute chewing test 30 min after infusions and day 4 and 7. Acidic saline induced higher pain intensity than control day 3 up to 5 min after infusions, but did not affect PPT. The chewing test did not evoke higher fatigue during chewing or MUO or after acidic saline infusion compared to control. Repeated acidic saline infusions in the masseter muscles induced a short-lasting muscle pain without mechanical hyperalgesia or functional pain. Hence, this model might not be superior to already existing experimental muscle pain models.

Can non-invasive brain stimulation augment the hypoalgesic effects of exercise?

Background: Exercise is the cornerstone of conservative management for persistent pain. While exercise is effective in the treatment of persistent pain, systematic reviews demonstrate, at best, small to moderate effects on pain. Thus, novel approaches that could enhance the hypoalgesic effects of exercise are warranted. Transcranial direct current stimulation (tDCS), a safe, painless non-invasive brain stimulation technique is capable of modulating pain processing and provides a promising avenue to boost the hypoalgesic response to exercise. Here, we explored whether the application of tDCS prior to a single bout of exercise would facilitate exercise-induced hypoalgesia in healthy individual's experiencing persistent experimental muscle pain.

Pain-Induced Reduction in Corticomotor Excitability Is Counteracted by Combined Action-Observation and Motor Imagery

Musculoskeletal pain reduces corticomotor excitability (CE) and methods modulating such CE reduction remain elusive. This study aimed to modulate pain-induced CE reduction by performing action observation and motor imagery (AOMI) during experimental muscle pain. Twelve healthy participants participated in 3 cross-over and randomized sessions separated by 1 week. During the AOMI session subjects performed an AOMI task for 10 minutes. In the AOMI+PAIN session, hypertonic saline was injected in the first dorsal interosseous muscle before performing the AOMI task. In the PAIN session, participants remained at rest for 10 minutes or until pain-resolve after the hypertonic saline injection. CE was assessed using transcranial magnetic stimulation motor-evoked potentials (TMS-MEPs) of the first dorsal interosseous muscle at baseline, during, immediately after, and 10 minutes after AOMI and/or PAIN. Facilitated TMS-MEPs were found after 2 and 4 minutes of AOMI performance (P < .017) whereas a reduction in TMS-MEPs occurred at 4 minutes (P < .017) during the PAIN session. Performing the AOMI task during pain counteracted the reduction in CE, as evident by no change in TMS-MEPs during the AOMI+PAIN session (P > .017). Pain intensity was similar between the AOMI+PAIN and PAIN sessions (P = .71). This study, which may be considered a pilot, demonstrated the counteracting effects of AOMI on pain-induced decreases in CE and warrants further studies in a larger population. PerspectiveThis is the first study to demonstrate a method counteracting the reduction in CE associated with acute pain and advances therapeutic possibilities for individuals with chronic musculoskeletal pain.

Effect of sustained experimental muscle pain on joint position sense.

Introduction:Joint position sense (JPS) is impaired in clinical musculoskeletal pain conditions, but when this impairment develops in the transition from initial to prolonged pain is not known.Objectives:This study assessed whether progressively developing sustained experimentally induced muscle pain impacts JPS in healthy individuals.Methods:Twenty-eight healthy individuals received injection of nerve growth factor (NGF) into the right extensor carpi radialis brevis muscle on days 0 and 2 to induce sustained pain and hyperalgesia. Wrist JPS was assessed 2 days before day 0 (day −2), before the injection on days 0 and 2, and on days 4 and 14. Joint position sense was quantified as the ability to return the wrist to a neutral position following movements in the direction of radial and ulnar deviation. A 3-dimensional motion analysis system was used to calculate absolute, relative, and joint-angle repositioning errors. Numerical rating scale scores of pain intensity, body chart pain drawings, and pressure pain thresholds (PPTs) were recorded on each day.Results:Compared with baseline, pressure pain thresholds decreased while pain intensity and area increased at day 2 (P < 0.001) and day 4 (P < 0.001) before returning to baseline on day 14 (P > 0.13). Relative to day 0, there was no change in wrist JPS at day 2, 4, and 14 following movements in either target direction (P > 0.05).Conclusion:Despite the presence of sustained muscle pain and hyperalgesia for 4 days at the elbow, no statistical change in wrist joint position error was observed. These findings suggest that pain and hyperalgesia lasting as long as 4 days does not impair JPS.

Experimental muscle pain of the vastus medialis reduces knee joint extensor torque and alters quadriceps muscle contributions as revealed through musculoskeletal modeling

BackgroundVoluntary activation deficit of the quadriceps muscle group is a common symptom in populations with knee joint injury. Musculoskeletal modeling and simulations can improve our understanding of pathological conditions; however, they are mathematically complex which can limit their clinical application. A practical subject-specific modeling framework is introduced to evaluate knee extensor inhibition and muscle force contributions to isometric knee joint torques in healthy adults with and without experimentally induced quadriceps muscle pain. MethodsA randomized cross-over placebo controlled study design was used. Subject-specific maximum knee joint extension torque and quadriceps electromyographic data from 13 uninjured young adults were combined in a modeling framework to determine optimal muscle strength scaling parameters and ideal torque. Strength deficit ratios (experimental torque/ideal torque) and individual muscle contribution to experimental torque was computed before and after intramuscular hypertonic (pain inducing) and isotonic (sham) saline was injected to the vastus medialis. FindingsDecreased experimental knee extension torque (−8%) and vastus medialis electromyography (−26%) amplitude pre- to post- hypertonic injection was observed. Correspondingly, significant decreases in the knee extensor strength deficit ratio (−18%) and percent contribution of vastus medialis to experimental torque (−24%) was observed pre- to post- hypertonic injection. No differences were observed with isotonic injections, confirming the validity of the model. InterpretationOur practical method to estimate strength ratios can be easily implemented within a musculoskeletal modeling framework to improve the validity of model estimates. This, in turn, can increase our understanding of the relationship between neuromuscular deficits and functional outcomes in patient populations.