HongLing Nie

Sensitization in patients with painful knee osteoarthritis

&NA; Pain is the dominant symptom in osteoarthritis (OA) and sensitization may contribute to the pain severity. This study investigated the role of sensitization in patients with painful knee OA by measuring (1) pressure pain thresholds (PPTs); (2) spreading sensitization; (3) temporal summation to repeated pressure pain stimulation; (4) pain responses after intramuscular hypertonic saline; and (5) pressure pain modulation by heterotopic descending noxious inhibitory control (DNIC). Forty‐eight patients with different degrees of knee OA and twenty‐four age‐ and sex‐matched control subjects participated. The patients were separated into strong/severe (VAS ≥ 6) and mild/moderate pain (VAS < 6) groups. PPTs were measured from the peripatellar region, tibialis anterior (TA) and extensor carpi radialis longus muscles before, during and after DNIC. Temporal summation to pressure was measured at the most painful site in the peripatellar region and over TA. Patients with severely painful OA pain have significantly lower PPT than controls. For all locations (knee, leg, and arm) significantly negative correlations between VAS and PPT were found (more pain, more sensitization). OA patients showed a significant facilitation of temporal summation from both the knee and TA and had significantly less DNIC as compared with controls. No correlations were found between standard radiological findings and clinical/experimental pain parameters. However, patients with lesions in the lateral tibiofemoral knee compartment had higher pain ratings compared with those with intercondylar and medial lesions. This study highlights the importance of central sensitization as an important manifestation in knee OA.

Contribution of the local and referred pain from active myofascial trigger points in fibromyalgia syndrome

ABSTRACT The generalized hypersensitivity associated with fibromyalgia syndrome (FMS) may in part be driven by peripheral nociceptive sources. The aim of the study was to investigate whether local and referred pain from active myofascial trigger points (MTrPs) contributes to fibromyalgia pain. FMS patients and healthy controls (n = 22 each, age‐ and gender‐matched) were recruited. The surface area over the upper trapezius muscle on each side was divided into 13 sub‐areas (points) of 1 cm in diameter for each point. Pressure pain threshold (PPT) and the local and referred pain pattern induced by manual palpation at 13 points bilaterally in the upper trapezius were recorded. Results showed that PPT levels at all measured points were significantly lower in FMS than controls. Multiple active MTrPs (7.4 ± 2.2) were identified bilaterally in the muscle in FMS patients, but no active MTrPs were found in controls. The mid‐fiber region of the muscle had the lowest PPT level with the largest number of active MTrPs in FMS and with the largest number of latent MTrPs in controls. The local and referred pain pattern induced from active MTrPs bilaterally in the upper trapezius muscle were similar to the ongoing pain pattern in the neck and shoulder region in FMS. In conclusion, active MTrPs bilaterally in the upper trapezius muscle contribute to the neck and shoulder pain in FMS. Active MTrPs may serve as one of the sources of noxious input leading to the sensitization of spinal and supraspinal pain pathways in FMS.

Delayed onset muscle soreness in neck/shoulder muscles

The aim of the present study is to: (1) induce delayed onset muscle soreness (DOMS) in the neck and shoulder muscles; (2) compare the pressure pain sensitivity of muscle belly with that of musculotendinous tissue after DOMS; (3) examine the gender differences in the development of DOMS. An eccentric shoulder exercise was developed to induce DOMS on neck/shoulder muscles using a specially designed dynamometer. Eccentric shoulder contraction consisted of 5 bouts, each bout lasted 3 min, with 3 min rest period between each bout. The right shoulder was elevating against a downward pressure force of 110% maximal voluntary contraction force exerted by the dynamometer. Pressure pain thresholds (PPT) of 11 sites (seven sites measured were muscle belly and four sites were myotendinous area) on neck/shoulder region were measured before, immediately after, 24 and 48 h after exercise. Pain intensity, pain area and index of McGill pain questionnaire were assessed and all were increased after exercise. DOMS was induced in the shoulder muscles. PPT was significantly decreased and reached lowest values at 24 h. The muscle belly sites are more sensitive to pain than the musculotendinous sites. No gender differences were found in any of the parameters used to assess the development of DOMS. DOMS did not distribute evenly in the neck/shoulder region. Soreness after exercise in the neck and shoulder seems not to be among the conditions that produce predominant musculoskeletal pain in females.

Spatial and temporal summation of pain evoked by mechanical pressure stimulation

Chronic pain patients often suffer from widespread and long lasting pain. The integrative effect of combined spatial and temporal summation on pain intensity has not been quantitatively tested. The present study was designed to investigate: (1) if the size of the stimulation area would facilitate the temporal summation of pain to repetitive pressure stimulation, and (2) if temporal summation is effective when stimulating separated sites, repetitively. Twenty healthy male subjects participated in this study. The test sites were located on the bilateral upper trapezius and tibialis anterior muscles. The ten stimuli (each with a duration of 1s) were applied to a single site at three inter‐stimulus intervals (ISI: 1, 5, 30s) using five different probe sizes (0.5, 1, 2, 4 and 8cm2). The stimulation intensity was equal to the pressure pain threshold (PPT) determined for each probe size. Similar repetitive stimulations at two inter‐stimulus intervals (5s and 30s) using two sizes of probes (0.5cm2 and 2cm2) were applied to ten separate sites. The PPT at the trapezius muscle decreased significantly with the increase in stimulus area from 0.5cm2 to 8cm2 (P<0.001) due to spatial summation. Temporal summation of pain was evoked by repetitive pressure stimuli on the same site for all ISI and was more pronounced at 5s and 30s ISI with larger probe areas (2, 4, and 8cm2) compared to smaller probe areas. There was no temporal summation of pain to stimuli with ISI 5 and 30s when stimulating the separated sites. The current study indicated that spatial summation facilitated the temporal summation of pain for stimuli given at 5s and 30s ISI. The combination of temporal and spatial integration of nociceptive input facilitates the pain intensity, suggesting that temporal summation is clinically relevant in conditions with widespread pain.

Mechanomyography and electromyography during and after fatiguing shoulder eccentric contractions in males and females.

The aim of this study was to investigate changes in mechanomyographic (MMG) and the surface electromyographic (EMG) signals during and after fatiguing shoulder eccentric contractions in a group consisting of 12 males and 12 females. Exerted force, MMG, EMG, pain and rate of perceived exertion were assessed before, during and after repeated high‐intensity eccentric exercises. Bouts of eccentric contractions caused a decrease in the exerted force for males (P<0.05) and an increase in the rate of perceived exertion and pain for both genders (P<0.05). During eccentric exercise, the root mean square (RMS) values of the MMG signal increased (P<0.05). The mean power frequency (MPF) values of the EMG signal decreased at the end of each eccentric bout for both genders (P<0.05); the decrease was higher for females compared with males (P<0.05). Immediately after eccentric exercise in static abduction of the upper limbs, the MMG RMS and MPF values increased (P<0.05). The present study showed that (1) neuromuscular changes associated with pain and changes in muscle stiffness and (2) changes in motor units strategy during fatigue development in shoulder muscle are reflected in the MMG and EMG signals.

The inter- and intra-individual variance in descending pain modulation evoked by different conditioning stimuli in healthy men

Abstract Background and purpose Conditioned pain modulation (CPM) is a phenomenon in which pain is inhibited by heterotopic noxious stimulation. It is not known how the experimental condition affects the magnitude of the CPM response and the inter-and intra-individual variations. It is important to get the information of the test–retest reliability and inter–individual variations of CPM to apply CPM as a diagnostic tool or for screening analgesic compounds. This study evaluated (1) the magnitude of CPM, (2) the inter-individual coefficient of variation (inter-CV) and (3) the intra-individual coefficient of variation (intra-CV) to (A) different stimulus modalities to evoke CPM and (B) different assessment sites. Methods Twelve healthy men (age 19–38 years) participated in this study. Cold pressor pain (CPP) (immersing the hand into cold water), tourniquet pain (cuff around the upper arm) and mechanical pressure pain (craniofacial region) were used in randomized order as conditioning stimuli (CS). The test stimulus (TS) was pressure pain applied to the right masseter muscle, left forearm and leg (bilateral tibialis anterior: TA). The responses were pressure pain thresholds (PPT), pressure pain tolerance (PPTol) thresholds and the pain intensity which was assessed on a visual analogue scale (VAS, 0–10 cm) following 1.4 and 1.6 × PPT applied to TA. The TS was applied before, during and 10 min after the CS. The intra-individual CV was estimated between different days. Results CPP induced the most powerful CPM on PPT (66.3 ± 10.0% increase), VAS ratings (41.5 ± 5.3% reduction) and PPTol (32.6±4.6% increase), especially at TA, and resulted in the smallest inter-CV (41.4–60.1%). Independently of the CS, the inter-CV in general showed that the recordings from the orofacial region and the forearm had smaller values than from the leg. The smallest intra-CV value was obtained in pain ratings with CPP (27.0%). Conclusions This study suggests that (1) the CPP evokes the largest CPM, (2) the leg as the assessment site results in the largest CPM responses and (3) the CPP causes the smallest inter- and intra-CV. Implication The present investigation implicates that the CPP is the most efficient conditioning stimulus to induce CPM when assessed by pressure pain thresholds.

Descending pain modulation and its interaction with peripheral sensitization following sustained isometric muscle contraction in fibromyalgia.

Sustained isometric muscle contraction (fatiguing contraction) recruits segmental and/or extrasegmental descending inhibition in healthy subjects but not in fibromyalgia (FM). We hypothesized that fatiguing contraction may shift descending pain modulation from inhibition towards facilitation and that the effect of descending pain modulation be dependent on peripheral muscle pain sensitivity.

Temporal summation of pressure pain during muscle hyperalgesia evoked by nerve growth factor and eccentric contractions

Nerve growth factor (NGF) has a key role in the generation and potentiation of pain. Its centrally sensitizing effects may facilitate pain responses to noxious stimulus. This study assessed (1) the influence of NGF on delayed onset muscle soreness (DOMS) in shoulder muscles; and (2) the temporal summation of pressure pain during hyperalgesia induced by NGF and DOMS. In a blinded design, 10 healthy subjects were injected with NGF in the trapezius muscle on one side and with isotonic saline on the contralateral side as control. The subjects undertook shoulder eccentric exercise to induce DOMS in the shoulder muscles 3h after the injections. The soreness intensity to muscle contraction, pressure pain thresholds (PPT), and pain intensity to sequential stimuli (i.e. temporal summation at 1 and 30s inter‐stimulus interval (ISI)) were assessed before injections −3, 24h, and 4, 7, and 21 days after injections. The soreness intensity to muscle contraction significantly increased at 3 and 24h in both shoulders (P<0.05) and went back to baseline levels at day 7. The same development was seen in PPT as reduced thresholds (P<0.05). The NGF injected side had higher pain ratings during temporal summation at 1s ISI compared with the contralateral side 24h after injections. Intramuscular administration of NGF intensified the DOMS responses, evoking facilitated temporal summation. Central as well as peripheral sensitization mechanisms may play a role in the facilitation.

Local pain and spreading hyperalgesia induced by intramuscular injection of nerve growth factor are not reduced by local anesthesia of the muscle

ObjectivesInjections with local anesthesia for therapeutic and diagnostic purposes are common clinical practice. This double-blind placebo controlled study explores the rational of local anesthetic blocks for the detection of muscle pain as the primary generator in spreading hyperalgesic conditions. MethodsExperimental muscle pain was induced by injections of nerve growth factor (NGF) in the left and right supraspinatus muscle of 11 healthy volunteers. One day later ropivacaine and saline were administered with ultrasound guidance in the left or right supraspinatus muscle in a randomized double-blind manner. Assessments before NGF, day 1 (before and after ropivacaine/saline), and day 7 included: visual analog scale (VAS) pain scores at rest and during shoulder shrugging, time until exercise interruption owing to pain, cutaneous pain sensitivity, pressure pain thresholds, and pain VAS during tonic pressure stimulation. Cutaneous and pressure pain sensitivity were assessed over the supraspinatus, infraspinatus, and deltoideus muscles, and at the web space between first and second finger. ResultsIncreased VAS pain scores and increased pressure pain sensitivity of the supraspinatus and infraspinatus muscles were found in both sides one day after the NGF injection compared with baseline. One day after NGF injections, the time until participants stopped exercising was reduced compared with baseline. The increased muscle pain sensitivity was not normalized by intramuscular ropivacaine. Saline caused increased VAS pain scores compared with ropivacaine. DiscussionMuscle pain and spreading hyperalgesia induced by NGF is maintained despite anesthesia of the primary nociceptive locus. This indicates that intramuscular injection of local anesthetics may not be a valid diagnostic method for primary muscle pain.

A human experimental bone pain model

or the mechanical threshold was affected by successive stimlations (517 ± 126, 413 ± 84, 598 ± 97 and 499 ± 122 g, for first o fourth stimulation, respectively) or differed between right and eft leg (522 ± 86 g vs. 492 ± 64 g, respectively). No correlations etween mechanical thresholds and behavioural responses were ound. onclusion: The results show that pigs respond behaviourally to echanical von Frey stimulation directed at the hind legs, and sugest that responses were not affected by successive stimulations.