Evoked oscillatory cortical activity during acute pain: Probing brain in pain by transcranial magnetic stimulation combined with electroencephalogram.

Temporal dynamics of local cortical rhythms during acute pain remain largely unknown. The current study used a novel approach based on transcranial magnetic stimulation combined with electroencephalogram (TMS-EEG) to investigate evoked-oscillatory cortical activity during acute pain. Motor (M1) and dorsolateral prefrontal cortex (DLPFC) were probed by TMS, respectively, to record oscillatory power (event-related spectral perturbation and relative spectral power) and phase synchronization (inter-trial coherence) by 63 EEG channels during experimentally induced acute heat pain in 24 healthy participants. TMS-EEG was recorded before, during, and after noxious heat (acute pain condition) and non-noxious warm (Control condition), delivered in a randomized sequence. The main frequency bands (α, ß1, and ß2) of TMS-evoked potentials after M1 and DLPFC stimulation were recorded close to the TMS coil and remotely. Cold and heat pain thresholds were measured before TMS-EEG. Over M1, acute pain decreased α-band oscillatory power locally and α-band phase synchronization remotely in parietal-occipital clusters compared with non-noxious warm (all p < .05). The remote (parietal-occipital) decrease in α-band phase synchronization during acute pain correlated with the cold (p = .001) and heat pain thresholds (p = .023) and to local (M1) α-band oscillatory power decrease (p = .024). Over DLPFC, acute pain only decreased ß1-band power locally compared with non-noxious warm (p = .015). Thus, evoked-oscillatory cortical activity to M1 stimulation is reduced by acute pain in central and parietal-occipital regions and correlated with pain sensitivity, in contrast to DLPFC, which had only local effects. This finding expands the significance of α and ß band oscillations and may have relevance for pain therapies.

Impact of Chronic Pain on Use-Dependent Plasticity: Corticomotor Excitability and Motor Representation in Musicians With and Without Pain.

Long-term musical training induces adaptive changes in the functional representation of the motor cortex. It is unknown if the maladaptive plasticity associated with chronic pain, frequently affecting trained musicians, may alter the use-dependent plasticity in the motor cortex. This study investigated the interaction between adaptive and maladaptive plasticity in the motor pathways, in particular how chronic pain influences long-term use-dependent plasticity. Using transcranial magnetic stimulation (TMS), corticospinal excitability was assessed by measuring the amplitude of the motor-evoked potential (MEP), area of the motor map, volume, and center of gravity of the first dorsal interosseous muscle in 19 pain-free musicians, 17 upper limb/neck pain chronic pain musicians, and 19 pain-free non-musicians as controls. Motor map volume and MEP amplitude were smaller for both pain-free and chronic pain musicians compared to pain-free controls (P < 0.011). No significant differences were found between musicians with and without chronic pain. These findings confirm that long-term musical training can lead to focalized and specialized functional organization of the primary motor cortex. Moreover, the adaptive use-dependent plasticity acquired through fine-motor skill acquisition is not significantly compromised by the maladaptive plasticity typically associated with chronic pain, highlighting the potential of long-term sensorimotor training to counteract the effects of chronic pain in the motor system.

Acute pain drives different effects on local and global cortical excitability in motor and prefrontal areas: insights into interregional and interpersonal differences in pain processing.

Pain-related depression of corticomotor excitability has been explored using transcranial magnetic stimulation-elicited motor-evoked potentials. Transcranial magnetic stimulation-electroencephalography now enables non-motor area cortical excitability assessments, offering novel insights into cortical excitability changes during pain states. Here, pain-related cortical excitability changes were explored in the dorsolateral prefrontal cortex and primary motor cortex (M1). Cortical excitability was recorded in 24 healthy participants before (Baseline), during painful heat (Acute Pain), and non-noxious warm (Warm) stimulation at the right forearm in a randomized sequence, followed by a pain-free stimulation measurement. Local cortical excitability was assessed as the peak-to-peak amplitude of early transcranial magnetic stimulation evoked potential, whereas global-mean field power measured the global excitability. Relative to the Baseline, Acute Pain decreased the peak-to-peak amplitude in M1 and dorsolateral prefrontal cortex compared with Warm (both P < 0.05). A reduced global-mean field power was only found in M1 during Acute Pain compared with Warm (P = 0.003). Participants with the largest reduction in local cortical excitability under Acute Pain showed a negative correlation between dorsolateral prefrontal cortex and M1 local cortical excitability (P = 0.006). Acute experimental pain drove differential pain-related effects on local and global cortical excitability changes in motor and non-motor areas at a group level while also revealing different interindividual patterns of cortical excitability changes, which can be explored when designing personalized treatment plans.

Level of pain catastrophising determines if patients with long-standing subacromial impingement benefit from more resistance exercise: predefined secondary analyses from a pragmatic randomised controlled trial (the SExSI Trial).

OBJECTIVE: The primary aim was to investigate the effectiveness of adding more resistance exercise to usual care on pain mechanisms (including temporal summation, conditioned pain modulation (CPM) and local pain sensitivity) and pain catastrophising in people with subacromial impingement at 16 weeks follow-up. Second, to investigate the modifying effect of pain mechanisms and pain catastrophising on the interventions' effectiveness in improving shoulder strength and disability METHODS: 200 consecutive patients were randomly allocated to usual exercise-based care or the same plus additional elastic band exercise to increase total exercise dose. Completed add-on exercise dose was captured using an elastic band sensor. Outcome measures recorded at baseline, 5 weeks, 10 weeks and 16 (primary end point) weeks included temporal summation of pain (TSP) and CPM assessed at the lower leg, pressure pain threshold at the deltoid muscle (PPT-deltoid), pain catastrophising and the Shoulder Pain and Disability Index. RESULTS: Additional elastic band exercise was not superior to usual exercise-based care in improving pain mechanisms (TSP, CPM and PPT-deltoid) or pain catastrophising after 16 weeks. Interaction analyses showed that pain catastrophising (median split) modified the effectiveness of additional exercises (effect size 14 points, 95% CI 2 to 25), with superior results in the additional exercise group compared with the usual care group in patients with less pain catastrophising. CONCLUSION: Additional resistance exercise added to usual care was not superior to usual care alone in improving pain mechanisms or pain catastrophising. Additional exercise was, however, superior in improving self-reported disability in patients with lower levels of pain catastrophising at baseline. TRIAL REGISTRATION NUMBER: NCT02747251.

Burst Transspinal Magnetic Stimulation Alleviates Nociceptive Pain in Parkinson Disease-A Pilot Phase II Double-Blind, Randomized Study.

BACKGROUND AND AIMS: Nociception is the most prevalent pain mechanism in Parkinson disease (PD). It negatively affects quality of life, and there is currently no evidence-based treatment for its control. Burst spinal cord stimulation has been used to control neuropathic pain and recently has been shown to relieve pain of nociceptive origin. In this study, we hypothesize that burst transspinal magnetic stimulation (bTsMS) reduces nociceptive pain in PD. MATERIALS AND METHODS: Twenty-six patients were included in a double-blind, sham-controlled, randomized parallel trial design, and the analgesic effect of lower-cervical bTsMS was assessed in patients with nociceptive pain in PD. Five daily induction sessions were followed by maintenance sessions delivered twice a week for seven weeks. The primary outcome was the number of responders (≥ 50% reduction of average pain intensity assessed on a numerical rating scale ranging from 0-10) during the eight weeks of treatment. Mood, quality of life, global impression of change, and adverse events were assessed throughout the study. RESULTS: Twenty-six patients (46.2% women) were included in the study. The number of responders during treatment was significantly higher after active than after sham bTsMS (p = 0.044), mainly owing to the effect of the first week of treatment, when eight patients (61.5%) responded to active and two (15.4%) responded to sham bTsMS (p = 0.006); the number needed to treat was 2.2 at week 1. Depression symptom scores were lower after active (4.0 ± 3.1) than after sham bTsMS (8.7 ± 5.3) (p = 0.011). Patients' global impressions of change were improved after active bTsMS (70.0%) compared with sham bTsMS (18.2%; p = 0.030). Minor adverse events were reported in both arms throughout treatment sessions. One major side effect unrelated to treatment occurred in the active arm (death due to pulmonary embolism). Blinding was effective. CONCLUSION: BTsMS provided significant pain relief and improved the global impression of change in PD in this phase-II trial. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT04546529.

Protocols for inducing homeostatic plasticity reflected in the corticospinal excitability in healthy human participants: A systematic review and meta-analysis.

Homeostatic plasticity complements synaptic plasticity by stabilising neural activity within a physiological range. In humans, homeostatic plasticity is investigated using two blocks of non-invasive brain stimulation (NIBS) with an interval without stimulation between blocks. The aim of this systematic review and meta-analysis was to investigate the effect of homeostatic plasticity induction protocols on motor evoked potentials (MEP) in healthy participants. Four databases were searched (Medline, Scopus, Embase and Cochrane library). Studies describing the application of two blocks of NIBS of the primary motor cortex with an interval of no stimulation between blocks reporting changes in corticospinal excitability by MEP amplitude were included. Thirty-seven reports with 55 experiments (700 participants) were included. Study quality was considered poor overall, with heterogeneity in study size, sample and designs. Two blocks of excitatory stimulation at the primary motor cortex produced a homeostatic response (decreased MEP) between 0 and 30 min post-protocols, when compared with a single stimulation block. Two blocks of inhibitory stimulation at the primary motor cortex using interval duration of 10 min or less produced a homeostatic response (increased MEP) between 0 and 30 min post-protocols, when compared with a single stimulation block. There were no differences in MEPs when compared with baseline MEPs. In conclusion, homeostatic plasticity induction using two blocks of NIBS with an interval of 10 min or less without stimulation between blocks produces a homeostatic response up to 30 min post-protocol. Improvements in participant selection, sample sizes and protocols of NIBS techniques are needed.

Aberrant plasticity in musculoskeletal pain: a failure of homeostatic control?

Aberrant synaptic plasticity is hypothesised to underpin chronic pain. Yet, synaptic plasticity regulated by homeostatic mechanisms have received limited attention in pain. We investigated homeostatic plasticity in the human primary motor cortex (M1) of 21 healthy individuals in response to experimentally induced muscle pain for several days. Experimental pain was induced by injecting nerve growth factor into the muscle belly of the right extensor carpi radialis brevis muscle. Pain and disability were monitored until day 21. Homeostatic plasticity was induced on day 0, 2, 4, 6, and 14 in the left M1 using anodal transcranial direct stimulation (tDCS) applied for 7 and 5 min, separated by a 3-min rest period. Motor-evoked potentials (MEP) to transcranial magnetic stimulation assessed the homeostatic response. On days 0 and 14, MEPs increased following the first block of tDCS (p < 0.004), and decreased following the second block of tDCS (p < 0.001), consistent with a normal homeostatic response. However, on days 2 (p = 0.07) and 4 (p = 0.7), the decrease in MEPs after the second block of tDCS was attenuated, representing an impaired homeostatic response. Findings demonstrate altered homeostatic plasticity in the M1 with the greatest alteration observed after 4 days of sustained pain. This study provides longitudinal insight into homeostatic plasticity in response to the development, maintenance, and resolution of pain over the course of 14 days.

Stimulus predictability moderates the withdrawal strategy in response to repetitive noxious stimulation in humans.

Nociceptive withdrawal reflex (NWR) is a protective reaction to a noxious stimulus, resulting in withdrawal of the affected area and thus preventing potential tissue damage. This involuntary reaction consists of neural circuits, biomechanical strategies, and muscle activity that ensure an optimal withdrawal. Studies of lower limb NWR indicate that the amplitude of the NWR is highly modulated by extrinsic and intrinsic factors, such as stimulation site, intensity, frequency, and supraspinal activity, among others. Whether the predictability of the stimulus has an effect on the biomechanical strategies is still unclear. This study aimed to evaluate how the predictability of impending noxious stimuli modulate the NWR reaction in the lower limb. NWR was evoked on fifteen healthy participants by trains of electrical stimuli on the sole of the foot and was measured in one distal (tibialis anterior) and one proximal (biceps femoris) muscle. The predictability was manipulated by giving participants prior information about the onset of the stimulus trains and the number of delivered stimuli per train. Results showed that the predictability of the incoming stimuli differentially modulates the muscle activity involved in the NWR reaction. For the most unpredictable stimulus train, larger NWR at distal muscles were evoked. Furthermore, the stereotyped temporal summation profile to repeated stimulation was observed when the stimulus train was completely predictable, while it was disrupted in proximal muscles in unpredictable conditions. It is inferred that the reflex response is shaped by descending control, which dynamically tunes the activity of the muscles involved in the resulting reaction.NEW & NOTEWORTHY Innate defensive behaviors such as reflexes are found across all species, constituting preprogrammed responses to external threats that are not anticipated. Previous studies indicated that the excitability of the reflex arcs like spinal nociceptive withdrawal reflex (NWR) pathways in humans are modulated by several cognitive factors. This study assesses how the predictability of a threat affects the biomechanical pattern of the withdrawal response, showing that distal and proximal muscles are differentially modulated by descending control.

Repeated Injections of Low-Dose Nerve Growth Factor (NGF) in Healthy Humans Maintain Muscle Pain and Facilitate Ischemic Contraction-Evoked Pain.

OBJECTIVE: Nerve growth factor (NGF) is essential for generating and potentiating pain responses. This double-blinded crossover study assessed NGF-evoked pain in healthy humans after repeated NGF injections in the tibialis anterior (TA) muscle compared with control injections of isotonic saline. SUBJECTS: Twenty healthy subjects participated in two experimental phases; each consisted of seven sessions over 21 days. METHODS: At day 0, day 2, and day 4, a low-dose NGF (1 µg) was injected. Data on daily self-reported muscle pain (using a Likert scale) were collected. Data on pressure pain thresholds (PPTs), pain evoked by nonischemic and ischemic muscle contractions (using a numerical rating scale [NRS]), pressure pain detection (PDT), and pain tolerance thresholds (PTTs) to cuff algometry were recorded before day 0 and at 1, 2, 4, 7, 10, and 21 days after the first injection. Temporal summation of pain (TSP) and conditioned pain modulation (CPM) were recorded to assess central pain mechanisms. RESULTS: Likert scores remained elevated for 9 days after NGF injection (P<0.05). PPTs at the TA muscle were decreased at day 1 until day 7 after NGF injection compared with day 0 (P=0.05). In subjects presenting with NGF-induced muscle hyperalgesia, pain NRS scores evoked by nonischemic contractions were higher after NGF injection at day 4 and day 7 (P<0.04) compared with the control condition. At all time points, higher pain NRS scores were found with ischemic compared with nonischemic contractions (P<0.05). The pain NRS after ischemic contractions was elevated following prolonged NGF hyperalgesia at day 7 compared with the control condition and day 0 (P<0.04). The PDT, PTT, TSP, and CPM remained unchanged during the period of NGF-induced hyperalgesia. CONCLUSIONS: Repeated low-dose NGF injections maintain muscle pain and potentiate pain evoked by ischemic contractions during prolonged NGF hyperalgesia.

The Effect of Stress on Repeated Painful Stimuli with and Without Painful Conditioning.

OBJECTIVES: Stress and pain have been interrelated in clinical widespread pain conditions. Studies indicate that acute experimental stress in healthy volunteers has a negative effect on the descending inhibitory pain control system and thus the ability to inhibit one painful stimulus with another (conditioned pain modulation [CPM]) although without effect on general pain sensitivity. CPM effects can be assessed immediately after the stress induction, whereas some physiological stress responses (e.g., cortisol release) are delayed and longer lasting. It is unclear whether CPM may relate to stress-induced increases in cortisol. DESIGN: Twenty-five healthy men had CPM effects measured over a period of 10 minutes. Pain detection thresholds (PDTs) were assessed by repeated test stimuli with cuff algometry on one leg, with and without painful cuff pressure conditioning on the contralateral leg. CPM effects, assessed as the increase in PDT during conditioning stimulation compared with without, were measured before and after experimental stress and a control condition (Montreal Imaging Stress Task [MIST]). Saliva cortisol levels and self-perceived stress were collected. RESULTS: Participants reported the MIST to be more stressful compared with the MIST control, but cortisol levels did not change significantly from baseline. In all sessions, PDT increased during conditioning (P = 0.001), although the MIST compared with the MIST control had no significant effect on PDT or CPM effects. A negative correlation between changes in cortisol and conditioned PDT was found when applying the MIST (P < 0.03). CONCLUSIONS: No significant effect of stress was found on CPM compared with a matched control condition. Individual changes in experimental stress and in conditioned pain sensitivity may be linked with cortisol.

Healthy Pain-Free Individuals with a History of Distal Radius Fracture Demonstrate an Expanded Distribution of Experimental Referred Pain Toward the Wrist.

OBJECTIVE: Nociception caused by injuries may sensitize central mechanisms causing expanded pain areas. After recovery, the status of such pain distribution and sensitivity mechanisms is unknown. The present study investigated whether individuals who have fully recovered from a distal radius fracture demonstrate increased pain sensitivity and expanded distribution of pressure-induced pain. DESIGN: Cross-sectional single-blinded study. SETTING: Clinical setting. SUBJECTS: Twenty-three pain-free individuals with a history of painful distal radius fracture and 22 nonfractured, age/gender-matched controls participated in two experimental sessions (day 0, day 1) 24 hours apart. METHODS: Pressure pain thresholds (PPTs) were recorded bilaterally at the extensor carpi radialis longus (ECRL), infraspinatus, and gastrocnemius muscles. Spatial distribution of pain was assessed following 60-second painful pressure stimulation at the ECRL (bilateral) and the infraspinatus muscles on the fractured or dominant side. Participants drew pain areas on a body map. After day 0 assessments, prolonged pain was induced by eccentric exercise of wrist extensors on the fractured/dominant side. RESULTS: Compared with controls, pressure-induced ECRL pain in the fracture group referred more frequently toward the distal forearm (P < 0.005) on day 0. Both groups showed larger pain areas on day 1 compared with day 0 (P < 0.005), although the fracture group showed a larger relative change between days (P < 0.005). The fracture group showed larger pain areas on the fracture side compared with the contralateral side on both days (P < 0.005). CONCLUSIONS: Prolonged pain and recovered prior painful injuries like fractures may sensitize pain mechanisms manifested as expanded pain distribution. Pressure-induced referred pain can be a simple pain biomarker for clinical use.

High frequency repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex modulates sensorimotor cortex function in the transition to sustained muscle pain.

Based on reciprocal connections between the dorsolateral prefrontal cortex (DLPFC) and basal-ganglia regions associated with sensorimotor cortical excitability, it was hypothesized that repetitive transcranial magnetic stimulation (rTMS) of the left DLPFC would modulate sensorimotor cortical excitability induced by muscle pain. Muscle pain was provoked by injections of nerve growth factor (end of Day-0 and Day-2) into the right extensor carpi radialis brevis (ECRB) muscle in two groups of 15 healthy participants receiving 5 daily sessions (Day-0 to Day-4) of active or sham rTMS. Muscle pain scores and pressure pain thresholds (PPTs) were collected (Day-0, Day-3, Day-5). Assessment of motor cortical excitability using TMS (mapping cortical ECRB muscle representation) and somatosensory evoked potentials (SEPs) from electrical stimulation of the right radial nerve were recorded at Day-0 and Day-5. At Day-0 versus Day-5, the sham compared to active group showed: Higher muscle pain scores and reduced PPTs (P < 0.04); decreased frontal N30 SEP (P < 0.01); increased TMS map volume (P < 0.03). These results indicate that muscle pain exerts modulatory effects on the sensorimotor cortical excitability and left DLPFC rTMS has analgesic effects and modulates pain-induced sensorimotor cortical adaptations. These findings suggest an important role of prefrontal to basal-ganglia function in sensorimotor cortical excitability and pain processing.

Corticomotor excitability reduction induced by experimental pain remains unaffected by performing a working memory task as compared to staying at rest.

Experimental pain inhibits primary motor cortex (M1) excitability. Attenuating pain-related inhibition of M1 excitability may be useful during rehabilitation in individuals with pain. One strategy to attenuate M1 excitability is to influence prefrontal and premotor cortex activity. Working memory tasks, e.g. the two-back task (TBT), engage prefrontal and premotor cortices and may influence M1 excitability. We hypothesized that performing the TBT during pain would influence pain-related changes in M1 excitability. Participants (n = 28) received rigorous training in the TBT before baseline testing. Experimental pain was induced by injecting hypertonic saline into the first dorsal interosseous (FDI) muscle. Participants rated pain intensity on a 0-10 numerical rating scale (NRS) every second min until pain-resolved (PR) during the performance of the TBT (n = 14) or during REST (n = 14). In the TBT, letters were presented pseudo-randomly, and accuracy and reaction time to identified letters corresponding to letters shown two times back were recorded. M1 excitability was assessed using transcranial magnetic stimulation. Motor-evoked potentials (MEPs) were recorded at baseline, and at PR, PR + 10, PR + 20, and PR + 30 min. Four minutes after hypertonic saline injection, the pain NRS scores were higher in the TBT group than the REST group (p = 0.009). No time × group interaction was found for MEPs (p = 0.73), but a main effect of time (p < 0.0005) revealed a reduction of MEPs at PR up until PR + 30 (p < 0.008). The TBT accuracy improved at PR + 30 in both groups (p = 0.019). In conclusion, the pain-induced reduction in corticomotor excitability was unaffected by performing a working memory task, despite greater pain in the TBT group.

Exercise-Induced Hypoalgesia After Isometric Wall Squat Exercise: A Test-Retest Reliabilty Study.

Background: Isometric exercises decrease pressure pain sensitivity in exercising and nonexercising muscles known as exercise-induced hypoalgesia (EIH). No studies have assessed the test-retest reliability of EIH after isometric exercise. This study investigated the EIH on pressure pain thresholds (PPTs) after an isometric wall squat exercise. The relative and absolute test-retest reliability of the PPT as a test stimulus and the EIH response in exercising and nonexercising muscles were calculated. Methods: In two identical sessions, PPTs of the thigh and shoulder were assessed before and after three minutes of quiet rest and three minutes of wall squat exercise, respectively, in 35 healthy subjects. The relative test-retest reliability of PPT and EIH was determined using analysis of variance models, Person's r, and intraclass correlations (ICCs). The absolute test-retest reliability of EIH was determined based on PPT standard error of measurements and Cohen's kappa for agreement between sessions. Results: Squat increased PPTs of exercising and nonexercising muscles by 16.8% ± 16.9% and 6.7% ± 12.9%, respectively (P < 0.001), with no significant differences between sessions. PPTs within and between sessions showed moderately strong correlations (r ≥ 0.74) and excellent (ICC ≥ 0.84) within-session (rest) and between-session test-retest reliability. EIH responses of exercising and nonexercising muscles showed no systematic errors between sessions; however, the relative test-retest reliability was low (ICCs = 0.03-0.43), and agreement in EIH responders and nonresponders between sessions was not significant (κ < 0.13, P > 0.43). Conclusions: A wall squat exercise increased PPTs compared with quiet rest; however, the relative and absolute reliability of the EIH response was poor. Future research is warranted to investigate the reliability of EIH in clinical pain populations.

Hypoalgesia after bicycling at lactate threshold is reliable between sessions.

PURPOSE: Exercise decreases pain sensitivity known as exercise-induced hypoalgesia (EIH). However, the consistency of EIH after an acute exercise protocol based on subjective ratings of perceived exertion has been questioned. Objectives were to compare the effect on pressure pain thresholds (PPTs) after bicycling with work-rate at the lactate threshold compared with quiet rest, and investigate between-session reliability of EIH. METHODS: Thirty-four healthy subjects completed three sessions with 7 days in-between. In session 1, the lactate threshold was determined via blood samples (finger-tip pinprick, > 2 mmol/l increase from warm-up) during a graded bicycling task. In session 2 and 3, all subjects performed (1) 15 min quiet-rest, and (2) 15 min bicycling (work-rate corresponding to the lactate threshold) in the two identical sessions. PPTs at the quadriceps and trapezius muscles were assessed before and after both conditions. Reliability was assessed by intraclass correlations (ICCs). RESULTS: Bicycling increased quadriceps PPT compared with quiet-rest in both sessions [mean difference: 45 kPa (95% CI 19-72 kPa), P = 0.002]; however, the increase in trapezius PPT was not significant after exercise. The EIH responses demonstrated fair between-session test-retest reliability (quadriceps: ICC = 0.45; trapezius: ICC = 0.57, P < 0.05), and agreement in EIH responders and non-responders between sessions was significant (quadriceps: κ = 0.46 and trapezius: κ = 0.43, P < 0.05). CONCLUSIONS: In conclusion, bicycling at the lactate threshold increased PPT at the exercising muscle with fair reliability of the local EIH response. The results have implications for future EIH studies in subjects with and without pain and for clinicians who design exercise programs for pain relief.

Experimental knee-related pain enhances attentional interference on postural control.

PURPOSE: To quantify how postural stability is modified during experimental pain while performing different cognitively demanding tasks. METHODS: Sixteen healthy young adults participated in the experiment. Pain was induced by intramuscular injection of hypertonic saline solution (1 mL, 6%) in both vastus medialis and vastus lateralis muscles (0.9% isotonic saline was used as control). The participants stood barefoot in tandem position for 1 min on a force plate. Center of pressure (CoP) was recorded before and immediately after injections, while performing two cognitive tasks: (i) counting forwards by adding one; (ii) counting backwards by subtracting three. CoP variables-total area of displacement, velocity in anterior-posterior (AP-velocity) and medial-lateral (ML-velocity) directions, and CoP sample entropy in anterior-posterior and medial-lateral directions were displayed as the difference between the values obtained after and before each injection and compared between tasks and injections. RESULTS: CoP total area ( - 84.5 ± 145.5 vs. 28.9 ± 78.5 cm2) and ML-velocity ( - 1.71 ± 2.61 vs. 0.98 ± 1.93 cm/s) decreased after the painful injection vs. Control injection while counting forward (P < 0.05). CoP total area (12.8 ± 53.9 vs. - 84.5 ± 145.5 cm2), ML-velocity ( - 0.34 ± 1.92 vs. - 1.71 ± 2.61 cm/s) and AP-velocity (1.07 ± 2.35 vs. - 0.39 ± 1.82 cm/s) increased while counting backwards vs. forwards after the painful injection (P < 0.05). CONCLUSION: Pain interfered with postural stability according to the type of cognitive task performed, suggesting that pain may occupy cognitive resources, potentially resulting in poorer balance performance.

Movement Does Not Promote Recovery of Motor Output Following Acute Experimental Muscle Pain.

Objective: To examine the effect of motor activity on the magnitude and duration of altered corticomotor output following experimental muscle pain. Design: Experimental, pre-post test. Setting: University laboratory. Subjects: Twenty healthy individuals. Methods: Participants were randomly allocated to a Rest or Movement group. The Rest group sat quietly without moving for the duration of the experiment. The Movement group repeated a unimanual pattern of five sequential keystrokes as quickly and as accurately as possible immediately following the resolution of pain. Pain was induced into the right extensor carpi radialis brevis muscle by a bolus injection of 0.5 mL hypertonic saline. Corticomotor output was assessed as motor evoked potentials in response to transcranial magnetic stimulation before, immediately after, and at 10, 20, and 30 minutes following pain resolution. Pain intensity was recorded every 30 seconds using an 11-point numerical rating scale. Results: There was no difference in peak pain intensity (P < 0.09) or duration (P < 0.2) between groups. Corticomotor output was reduced in both groups (P < 0.002) at 10 minutes (P < 0.002), 20 minutes (P < 0.02), and 30 minutes (P < 0.037) following the resolution of pain relative to baseline. There was no difference between groups at any time point. Conclusions: Performance of motor activity immediately following the resolution of acute muscle pain did not alter the magnitude or duration of corticomotor depression. Understanding corticomotor depression in the postpain period and what factors promote recovery has relevance for clinical pain syndromes where ongoing motor dysfunction, in the absence of pain, may predispose to symptom persistence or recurrence.

Light Touch Contact Improves Pain-Evoked Postural Instability During Quiet Standing.

Objective: To investigate if attention to additional sensory information from the fingertip can improve postural stability during pain, which is known to impair balance. Methods: In 16 healthy volunteers, experimental pain was induced by intramuscular injection of hypertonic saline in the right vastus medialis muscle (isotonic saline used as nonpainful control, intramuscular injection in the same location). Pain intensity was assessed on an 11-point numeric rating scale (NRS; 0 representing "no pain" and 10 "maximum pain"). Subjects were asked to stand as still as possible on a force plate for 40 seconds with their eyes closed. Their postural stability was quantified by the area and velocity of center of pressure (CoP) displacement. The CoP was recorded with and without pain during two different conditions: 1) no touch and 2) the subjects were asked to lightly touch a curtain with their right index finger and focus their attention on keeping it as still as possible. Results: Hypertonic injections induced higher NRS scores compared with control injections (P < 0.05). During the hypertonic injection condition, the CoP area and velocity in both directions increased during no touch compared with the light touch condition (P < 0.05). No differences were found during light touch between the hypertonic and isotonic injection conditions. Although experimental knee-related pain impaired postural stability, lightly touching a curtain with the fingertip decreased postural sway during painful conditions. Conclusions: Providing additional sensory information while pain patients are performing balance exercises may improve postural stability and increase the quality of exercise, consequent rehabilitation protocols, and clinical outcomes.

Test-Retest Reliabilty of Exercise-Induced Hypoalgesia After Aerobic Exercise.

Objective: Exercise increases pressure pain thresholds (PPTs) in exercising and nonexercising muscles, known as exercise-induced hypoalgesia (EIH). No studies have investigated the test-retest reliability of change in PPTs after aerobic exercise. Primary objectives were to compare the effect on PPTs after an incremental bicycling exercise compared with quiet rest and to investigate the relative and absolute test-retest reliability of the test stimulus (PPT) and the absolute and relative EIH response in exercising and nonexercising muscles. Setting: Laboratory. Methods: In two sessions, PPTs in the quadriceps and trapezius muscles were assessed before and after 15 minutes of quiet rest and 15 minutes of bicycling in 34 healthy subjects. Habitual physical activity was assessed by the International Physical Activity Questionnaire (IPAQ). Results: Bicycling increased PPTs in exercising and nonexercising muscles in both sessions (P < 0.05). The magnitude of the EIH response in the exercising muscle was, however, larger in the second compared with the first session (P < 0.015). PPTs showed excellent (intraclass correlation [ICC] ≥ 0.84) within-session and between-session test-retest reliability. The EIH response in exercising and nonexercising muscles demonstrated fair (ICC = 0.45) between-session relative test-retest reliability, but agreement in EIH responders between sessions was not significant (quadriceps: κ = 0.24, P = 0.15; trapezius: κ = 0.01, P = 0.97). Positive correlations between the IPAQ score and PPTs were found (quadriceps: r = 0.44, P = 0.009; trapezius: r = 0.31, P = 0.07) before exercise. No significant association was found between IPAQ and EIH. Conclusions: Incremental bicycling exercise increased PPTs with fair relative and absolute reliability of the EIH response. These data might have an impact on future studies investigating EIH and for clinicians designing exercise programs for pain relief.

Differential Corticomotor Excitability Responses to Hypertonic Saline-Induced Muscle Pain in Forearm and Hand Muscles.

Experimental muscle pain inhibits corticomotor excitability (CE) of upper limb muscles. It is unknown if this inhibition affects overlapping muscle representations within the primary motor cortex to the same degree. This study explored CE changes of the first dorsal interosseus (FDI) and extensor carpi radialis (ECR) muscles in response to muscle pain. Participants (n = 13) attended two sessions (≥48 hours in-between). Hypertonic saline was injected in the ECR (session one) or the FDI (session two) muscle. CE, assessed by transcranial magnetic stimulation (TMS) motor-evoked potentials (MEPs), was recorded at baseline, during pain, and twenty minutes postinjection together with pain intensity ratings. Pain intensity ratings did not differ between the two pain sites (p = 0.19). In response to FDI muscle pain, the MEPs of the FDI muscle were reduced at 2 and 4 min postinjection (p ≤ 0.03), but not after ECR muscle pain. No significant MEP change was detected for the ECR muscle (p = 0.62). No associations between MEPs and pain intensity were found (p > 0.2). The present results indicate that the output from overlapping cortical representations of two muscles differentially adapts to acute muscle pain.