Induction and modulation of referred muscle pain in humans

Muscle pain is a major factor in many disorders such as injuries, degenerative diseases, and cancer. The mechanisms underlying muscle pain are not fully understood. A particular problem in muscle pain is the relationship between local and referred muscle pain. Experimental pain models are useful in basic pain research, because they allow a standardized activation of the nociceptive system and measurements of evoked responses. An electrical muscle pain model was constructed and applied on healthy subjects. The model was found suitable for inducing local (LP) and referred muscle pain (RF). It was demonstrated that LP was elicited around the stimulation needles (proximal part of the tibial anterior muscle) and RP appeared at a distal site (the ventral part of the ankle). RP required significantly higher stimulus intensity compared with LP, and RP appeared later than LP. The sizes of LP and RP areas were correlated to pain intensity, and LP and RP thresholds were reproducible within and between sessions. Experimentally (electrical stimulation and infusion of hypertonic saline) induced muscle pain seems to be mediated by myelinated and unmyelinated afferents and the peripheral component of RP by myelinated afferents. Furthermore, cutaneous anesthesia of the RP area resulted in a reduction of RP intensity of 22%, while a complete nerve block of afferents from the RP area resulted in a 40% reduction. In summary, observations from the presented experiments suggest that elicitation of referred muscle pain is depending on and correlated to local muscle pain. Peripheral input from the RP area is involved, but is not a necessary condition for RP to appear. The present studies as well as others suggest that central hyperexcitability is involved in the generation of RP, but further investigations on mechanisms of RP are needed. Spinal cord and higher centers are likely structures to study. The data presented in this thesis have made further contributions to understanding the mechanisms of muscle pain and RP that can be helpful in diagnosis, control, and treatment of muscle pain. Moreover, the intramuscular, electrical pain model may be helpful in future clinical studies when aspects of muscle pain are investigated.