Shift work, inflammation and musculoskeletal pain-The HUNT Study.

BACKGROUND: Studies have indicated that shift work, in particular night work, is associated with chronic musculoskeletal pain but the mechanisms are unclear. It has been suggested that sleep disturbance, a common complaint among shift and night workers, may induce low-grade inflammation as well as heightened pain sensitivity. AIMS: Firstly, this study was aimed to examine the cross-sectional associations between shift work, C-reactive protein (CRP) level and chronic musculoskeletal pain, and secondly, to analyse CRP as a mediator between shift work and chronic musculoskeletal pain. METHODS: The study included 23 223 vocationally active women and men who participated in the HUNT4 Survey of the Trøndelag Health Study (HUNT). Information was collected by questionnaires, interviews, biological samples and clinical examination. RESULTS: Regression analyses adjusted for sex, age and education revealed significant associations between shift work and odds of any chronic musculoskeletal pain (odd ratio [OR] 1.11, 95% confidence interval [CI] 1.04-1.19), between shift work and CRP level (OR 1.09, 95% CI 1.03-1.16) and between CRP level 3.00-10 mg/L and any chronic musculoskeletal pain (OR 1.38, 95% CI 1.27-1.51). Shift work and CRP were also associated with number of chronic pain sites. Mediation analysis indicated that shift work was indirectly associated with any chronic musculoskeletal pain through CRP (OR 1.03, 95% CI 1.01-1.06). CONCLUSIONS: The results support the hypothesis that shift work is associated with chronic musculoskeletal pain, and that systemic inflammation may be a biological mechanism linking shift work to chronic pain.

Experimental sleep restriction increases latency jitter in pain elicited cortical responses.

OBJECTIVE: Previous studies have shown increased pain scores to painful stimulation after experimental sleep restriction, but reduced or unchanged magnitude of the event related potentials (ERPs) when averaged in the time-domain. However, some studies found increased response magnitude when averaging in the time-frequency domain. The aim of this study was to determine whether ERP-latency jitter may contribute to this discrepancy. METHODS: Ninety painful electrical stimuli were given to 21 volunteers after two nights of 50% sleep restriction and after two nights of habitual sleep. ERPs were analyzed in the time-domain (N2-and P2-peaks) and time-frequency domain (power spectral density). We quantified latency jitter by the mean consecutive difference (MCD) between single-trial peak latencies and by phase locking value (PLV) across trials. RESULTS: P2-MCD increased from 20.4 ± 2.1 ms after habitual sleep to 24.3 ± 2.2 ms after sleep restriction (19%, p = 0.038) and PLV decreased from 0.582 ± 0.015 after habitual sleep to 0.536 ± 0.015 after sleep restriction (7.9%, p = 0.009). We found no difference for N2-MCD. CONCLUSIONS: Our results indicate that partial sleep restriction increase latency jitter in cortical responses to experimental pain. SIGNIFICANCE: Latency jitter may contribute to the discrepancies between ERP-responses in the time-frequency domain and time-domain. Latency jitter should be considered when ERPs are analyzed.

Exploration of conditioned pain modulation effect on long-term potentiation-like pain amplification in humans.

BACKGROUND: This study aimed to explore conditioned pain modulation (CPM) effect on long-term potentiation (LTP)-like pain amplification induced by cutaneous 10-Hz conditioning electrical stimulation (CES). METHODS: Conditioned pain modulation was induced by cold pressor conditioning stimulus (CPCS) (4 °C) which was applied immediately before CES in the active session. In the control session, water with a temperature of 32 °C was used. Twenty subjects participated in two sessions in a randomized crossover design with at least 1-week interval. Perceptual intensity ratings to single electrical stimulation (SES) at the conditioned skin site and to pinprick and light-stroking stimuli in the immediate vicinity of the CES electrodes were measured . Superficial blood flow (SBF), skin temperature (ST) and heat pain threshold (HPT) were measured covering both homotopic and heterotopic skin. The pain intensities during CES process were measured and short-form McGill Pain Questionnaire (SF-MPQ) was used for assessing CES pain experience. RESULTS: Cold pressor conditioning stimulus reduced pain perception increments to weak pinprick and light-stroking stimuli after 10-Hz CES compared with the control session. Moreover, CPCS resulted in lower pain intensity ratings during CES process but without affecting the SF-MPQ scores between two sessions. The SBF and ST increased after CES and then gradually declined but without differences between CPCS and control sessions. CPM did not affect HPT and pain intensity increments to SES. CONCLUSIONS: The CPCS inhibited heterotopic perception amplification to weak mechanical stimuli after CES. The results indicate that endogenous descending inhibitory systems might play a role against development of non-nociceptive perception amplificatory states (e.g. allodynia). SIGNIFICANCE: Conditioned pain modulation (CPM) may play a role in inhibiting the pain amplificatory process at the central nervous system and prompting central desensitization. CPM has a special inhibition effect for the development of perception amplification to non-painful mechanical stimuli.

Conditioned pain modulation is not decreased after partial sleep restriction.

BACKGROUND: Sleep problems have been identified as a risk factor for several chronic pain conditions. Reduced sleep has been related to increased pain perception and it has been hypothesized that reduced pain inhibition may explain this. The aim of this study was to determine if sleep restriction (SR) affects heat pain perception and conditioned pain modulation (CPM). METHODS: In a paired cross-over design with two conditions (2 nights habitual sleep (HS) vs. 2 nights 50% SR) CPM was tested in 22 healthy individuals (14 women, 8 men). The test stimulus (TS) was 2-min contact heat stimulation (47  ± 1.3  °C) to the volar forearm. TS was delivered before and during a 7 °C cold pressor test (conditioning stimulus, CS) to the contralateral hand. RESULTS: TS was perceived as more painful after SR compared to after HS (p < 0.001). A stronger inhibitory CPM was found after SR versus after HS (p < 0.001). CONCLUSIONS: The results indicate that SR leads to increased heat pain perception, but not reduced inhibitory CPM. This contradicts general assumptions on the relation between SR and the CPM effect.

Recommendations on practice of conditioned pain modulation (CPM) testing.

Protocols for testing conditioned pain modulation (CPM) vary between different labs/clinics. In order to promote research and clinical application of this tool, we summarize the recommendations of interested researchers consensus meeting regarding the practice of CPM and report of its results.

A large conditioned pain modulation response is not related to a large blood pressure response: a study in healthy men.

BACKGROUND: Endogenous pain modulation has been studied with the conditioned pain modulation (CPM) paradigm with large differences in the magnitude of the CPM effect. We hypothesized that differences in CPM effects might be associated with differences in blood pressure responses to the conditioning stimulus when comparing the CPM effects using two different conditioning stimuli. METHODS: A single-blind repeated-measures design with block-randomization was applied on 25 healthy male subjects. The test stimulus (TS; tonic heat pain for 120 s) was first presented alone, thereafter in parallel with a conditioning stimulus (CS). Conditioning stimuli were either a cold pressor test (CPT) or equally painful ischaemic muscle pain (ISC), both lasting 120 s. Finger blood pressure and heart rate were recorded continuously. Data were analysed in a linear mixed model framework with CS type (CPT or ISC) and conditioning (TS or TS + CS) as independent factors. RESULTS: An inhibitory CPM effect was found for both types of conditioning (p < 0.001). The CPM effect was larger during CPT conditioning compared with ISC conditioning (p = 0.001). No association with the concomitant cardiovascular response (blood pressure and heart rate) was found (p > 0.34). CONCLUSION: Cold pressor pain CS induces larger CPM effects than ischaemic pain CS. The larger CPM effect is, however, not associated with a larger blood pressure response. Other factors related to the CS should be investigated to understand why different CS modalities give different CPM effects.

An inhibitory interaction of human cortical responses to stimuli preferentially exciting Adelta or C fibers.

Finely myelinated (type Adelta) and unmyelinated (type C) fibers are the major afferent inputs to spinothalamic tract neurons mediating sensory and reflex responses to noxious and thermal stimuli. These two fiber types differ in their sensory and biophysical properties, raising questions about the interaction of their supraspinal responses. Therefore, we investigated the interaction of cortical responses to stimuli that preferentially excite these fibers in human subjects using evoked potential recordings in a paired conditioning stimulation (CS) and test stimulation (TS) paradigm. There were two experiments, one with Adelta as CS and C as TS (Adelta-C) and another with these stimuli reversed (C-Adelta). We used intra-epidermal electrical pulses applied to the dorsal left hand at 2x and 1x pinprick threshold (pp) for the preferential stimulation of Adelta fibers and 37-50 degrees C contact heat pulses applied to the left or right thenar and left hypothenar eminences for the preferential stimulation of C fibers. We found that the cortical response to preferential Adelta or C fiber stimulation was attenuated whenever either cortical response preceded the other. Standardized values of peak and integrated amplitudes were <1 in all pairing conditions and in all subjects in both experiments. The suppressive effect varied in magnitude with the intensity of the conditioning stimulus in both Adelta-C and C-Adelta experiments. Furthermore, intra-segmental interaction was differentially effective for Adelta conditioning (peak amplitude, P<0.008; analysis of variance). Our experiments provide the first neurophysiological evidence for a somatotopically distributed, mutually suppressive interaction between cortical responses to preferentially activated Adelta and C afferents in humans. This suppressive interaction of cortical responses suggests contrasting and possibly mutually exclusive sensorimotor functions mediated through the Adelta and C fiber afferent channels.

Sympathetic nerve activity does not reduce proprioceptive acuity in humans.

AIM: Proprioception is essential in coordinating body segments and controlling muscles to perform movements. Animal studies have reported reduced muscle spindle sensitivity in jaw muscles during stimulation of sympathetic nerves. A stress-induced distortion of proprioception has been suggested that could lead to reduced fine control of movement and inefficient muscle use. The present study investigated whether increased muscle sympathetic activation alter human proprioception. METHOD: Movement detection thresholds of the right ankle were determined in eight healthy subjects, before and during two conditions known to increase muscle sympathetic activity (MSA); a cold pressor test (CPT) and oral glucose ingestion (GLUC). RESULTS: During a cold pressor test plasma noradrenaline (NA) and mean arterial pressure (MAP) increased significantly, compared with baseline (Ps<0.01), whereas the movement thresholds were unchanged (Ps>>0.05). After GLUC plasma NA and MAP increased significantly, compared with baseline (Ps<0.05). The movement threshold into flexion decreased (P=0.022), whereas into extension there was no change (P=0.28). The most prominent increase of plasma NA corresponded with a reduced movement detection threshold, suggesting increased muscle spindle sensitivity. CONCLUSION: The present findings contradict previous reports from animal studies and the hypothesis that sympathetic nerve activity reduces proprioceptive acuity.

The influence of experimental muscle pain on the human soleus stretch reflex during sitting and walking.

OBJECTIVES: The stretch reflex is functionally important during human locomotion. Muscle pain has been found to increase the stretch reflex amplitude during sitting, possibly due to an altered fusimotor drive. To further study the importance of altered fusimotor activity due to muscle pain we investigated the combined effect of muscle pain and motor task on the soleus stretch reflex. METHODS: Stretch reflexes were elicited before, during and after experimentally induced muscle pain in soleus (i.m. infusion of 6% saline) in 3 experiments: (1) in the relaxed soleus muscle and before, during and after an isometric ramp contraction (500 ms, 0-10 Nm), (2) at 3 different time periods during walking, and (3) at matched pain intensity and soleus activity during sitting and walking. RESULTS: Infusion of hypertonic saline into the soleus muscle caused a significant facilitated stretch reflex in the relaxed muscle (P<0.01), but not during walking or during sitting and walking at matched soleus EMG and matched pain levels. The infusion of isotonic saline (non-painful) did not cause any changes (P = 0.75). CONCLUSIONS: The main findings of the present study were that experimental muscle pain facilitated the stretch reflex during pain in the relaxed muscle, but caused no changes in stretch reflex amplitude during sitting and walking at higher "functional" background EMG levels.

Experimental muscle pain does not cause long-lasting increases in resting electromyographic activity.

The mutual links between muscle pain and resting electromyographic (EMG) activity are still controversial. This study described effects of experimental muscle pain on resting EMG activity in a jaw-closing muscle and a leg muscle. Pain was induced by injections of hypertonic saline into the muscles in 10 subjects. Injections of isotonic saline served as a control. The pain intensity was scored on visual analog scales (VAS) and surface and intramuscular wire EMGs were obtained from the resting muscles before, during, and after saline injections. EMG activity was analyzed in 30-s intervals and demonstrated, in both muscles, significant increases 30-60 s after injection of hypertonic saline, but not after injection of isotonic saline. In contrast to the transient increase in EMG activity, the pain sensation lasted up to 600 s after injection of hypertonic saline. It was concluded that acute muscle pain is unable to maintain longer-lasting resting muscle hyperactivity.

Experimental muscle pain increases the human stretch reflex.

In this study we investigated the effect of human experimental muscle pain on H- and stretch reflexes as indicators of changes in muscle spindle sensitivity. Fourteen healthy, male volunteers participated in the study. Muscle pain was produced by infusion of 5% hypertonic saline over a period of 10-15 min in m. soleus and in m. tibialis anterior. Reflexes were elicited in the relaxed and active soleus muscle (10-15 Nm ankle torque) before, during and after muscle pain. Control measurements were made with infusions of 0.9% isotonic saline. Surface electromyograms (EMG) were measured from the soleus muscle, and torque was measured from the ankle joint. With pain in the soleus muscle the mechanical stretch reflex response (ankle torque) increased significantly (P = 0.0007) as compared to before pain. With pain in the tibialis anterior muscle both the mechanical and EMG responses increased significantly (P = 0.001; P = 0.0003) as compared to before pain. The H-reflex showed no significant changes during the infusions in either muscles. This study has demonstrated a muscle pain-related increase in the amplitude of the stretch reflex without a corresponding increase in the H-reflex amplitude. One explanation could be an increased dynamic sensitivity of the muscle spindles during muscle pain caused by an increased firing rate in the dynamic gamma-motoneurones. However, the data could not support the vicious cycle model because the excitability of the alpha-motoneurone pool was unchanged.