Dagfinn Matre

Experimental muscle pain increases the human stretch reflex

&NA; 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 &ggr;‐motoneurones. However, the data could not support the vicious cycle model because the excitability of the &agr;‐motoneurone pool was unchanged.

Placebo effects in laser-evoked pain potentials

Placebo treatment may affect multiple components of pain, including inhibition of nociceptive input, automatic or deliberative appraisal of pain, or cognitive judgments involved in pain reporting. If placebo analgesia is due in part to an attenuation of early nociceptive processing, then pain-evoked event-related potentials (ERPs) should be reduced with placebo. In this study, we tested for placebo effects in P2 laser-evoked potentials at midline scalp electrodes. We found that placebo treatment produced significant decreases in P2 amplitude, and that P2 placebo responses were large enough to reflect a meaningful difference in nociceptive processing. However, we also found evidence that the very robust placebo-induced decreases in reported pain are not solely explained by early reductions in P2. N2 amplitude was affected by neither placebo nor reduction of laser intensity. These results suggest that placebo treatment affects early nociceptive processing, but that another component of placebo effects in reported pain occurs later, either in evaluation of pain or cognitive judgments about pain reports.

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.

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.

Effects of localization and intensity of experimental muscle pain on ankle joint proprioception

Accurate proprioceptive input is a prerequisite for balance control and coordination of movement. The present study investigated whether experimental muscle pain induced in healthy human subjects disturbed movement sense (detection of movement) or position sense (recognition of a reference position). Muscle pain was produced by infusion of 6% hypertonic saline simultaneously in m. tibialis anterior (TA) and m. soleus (experiment 1), by infusion of 6% hypertonic saline in TA (experiment 2) and by infusion of 9% hypertonic saline in TA (experiment 3). Control measurements were done with infusions of 0.9% isotonic saline. All infusions of 6% and 9% saline produced pain intensities significantly higher than the corresponding control infusions. Only infusion of 6% saline in two muscles (visual analogue scale = 4–5) produced an elevation in movement detection thresholds which was significantly higher, compared with before infusion. No other significant changes in movement and position sense were found during the painful or control infusions. Pain of relatively high intensity in two antagonist muscles is necessary to disturb the movement detection threshold. The ability to recognize a reference position is not disturbed by experimentally induced muscle pain. Whether the disturbed movement sense is caused by sensitivity changes in muscle spindle afferents or altered processing of proprioceptive input cannot be answered. The present findings indicate that human ankle proprioception is rather robust to muscle pain.

Interaction between cutaneous and muscle afferent activity in polysynaptic reflex pathways: a human experimental study.

Abstract Interactions between the input from cutaneous and nociceptive muscle afferents in polysynaptic reflex pathways were investigated in man. Interaction was tested by evoking reflexes before, during, and after a period of muscle pain induced by intramuscular injection of hypertonic saline. Muscle pain was induced either in the ankle flexor (tibialis anterior, TA) or in the extensor (soleus, SOL) muscles by injection of 1 ml hypertonic saline. Electrical skin stimulation (1.1×initial reflex threshold) at the dorsum of the foot over the tarsal joint was used to elicit cutaneo‐muscular polysynaptic reflexes in the knee flexor semitendinosus (ST). The injected hypertonic saline evoked a robust muscle pain (the subjects made a continuous score of the muscle pain on a 0–10 cm VAS scale, and the mean VAS area was 1229±251 cm×s and lasting 390±30 s). In five of 12 subjects, the infusion of hypertonic saline into TA evoked referred pain to the dorsal aspect of the ankle. A significant inhibition (17±8.2%, P<0.05) of the ST‐reflex by pain in SOL was observed. Pain in TA facilitated (92±36%, P<0.05) the short‐latency part (50–70 ms post stimulation) of the reflex. The muscle pain did not modulate the perceived sensory intensity of the electrical stimuli. The findings indicate an interaction of input from thin muscle afferents and cutaneous group A‐fibre afferents in polysynaptic segmental reflex pathways, which seems to depend on the location of the muscle pain.

Conditioned pain modulation is not decreased after partial sleep restriction

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).

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

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.

Conditioned pain modulation (CPM) is not one single phenomenon – Large intra-individual differences depend on test stimulus (TS) and several other independent factors

Through a relatively well-characterized network, our body is ble to regulate nociceptive processing to produce either facilitaion or inhibition of the pain experience [2]. Put simply, facilitation f nociceptive activity will produce more intense pain, and inhiition will produce less pain. Increased pain inhibitory activity ay be necessary during stress or the need to escape from threat. ncreased pain facilitatory activity may be useful during recuperaion from injury by producing hyperalgesia or allodynia around the njured tissue, reducingmovement and promoting healing. Clearly, physiological system with pain modulating capabilities is of outost importance.

Induction of the perceptual correlate of human long-term potentiation (LTP) is associated with the 5-HTT genotype

The purpose of the present study was to examine how genetic variability in the promoter of the SLC6A4 gene encoding the serotonin transporter (5-HTT) may influence induction of long-term potentiation (LTP). The genotyping of the 53 healthy volunteers was performed by a combination of TaqMan assay and gel electrophoresis. Based on the transcription rates, the subjects were divided in 3 groups; 5-HTT SS, 5-HTT SL(G)/L(A)L(G)/SL(A) and 5-HTT L(A)L(A). The intensity of pain to test stimuli was rated on a visual analog scale (VAS). High frequency stimulation (HFS) conditioning applied to one arm was used to induce LTP. Only a minor change in pain was observed following the HFS conditioning evoked by electrical test stimuli delivered through the conditioning electrode. Moreover, the change in pain evoked by test stimuli delivered through the conditioning electrode was not related to the 5-HTT genotype. However, we observed a clear increase in pain following the HFS conditioning evoked by mechanical pin-prick test stimuli delivered at the skin adjacent to the conditioning. Also, the 9 individuals with the 5-HTT SS genotype reported more pain than individuals with 5-HTT SL(G)/L(A)L(G)/SL(A) genotype following HFS conditioning on mechanical pin-prick test stimuli. Thus, the present data show that induction of the perceptual correlate of human LTP is associated with the genetic variability in the gene encoding the 5-HTT. Taken together, this suggests that the expression of 5-HTT, may be important for induction of LTP in humans.