Acute experimental muscle pain : spatiotemporal expression of local and referred pain in human subjects

Abstract

Each and every scientific observation is precisely defined by the state of the variables affecting the observed system. In this respect the choice and validation of a given experimental model is as important as the as the observations recorded. This thesis presents a series of studies utilising and developing the model of hypertonic saline induced human muscle pain to further our understanding of the peripheral and central spatiotemporal characteristics of local and referred pain. In the first three studies an adaptation of the classical (Kellgren 1938) model of hypertonic induced muscle pain utilises increased sample frequency to quantify the percept of local and referred pain; in the absence of local pain; over the course of multiple stimuli within the same subjects and between different limbs with differing stimuli intensities. In the last study we utilise functional magnetic resonance imaging to characterise somatotopy of pain from this model within the human insula. The first study examines the effects of local pain blockade on the expression of local and referred pain. This chapter is based on a publication in Journal of Pain titled "Effects of Intramuscular Anaesthesia on the Expression of Primary and Referred Pain Induced by Intramuscular Injection of Hypertonic Saline"- (Rubin, Gandevia et al. 2009). Intramuscular injection of hypertonic saline produces pain in the belly of the injected muscle (primary pain) and, pain that projects distally (referred pain). While it is known that referred pain can be induced during complete sensory block of the distal site, there is little evidence as to whether the perception of referred pain depends on ongoing input from the primary stimulus. We assessed whether blocking the noxious input following the induction of pain blocks the primary but not the referred pain. In all subjects, the area and intensity of primary pain rapidly disappeared within 7.5 minutes of intramuscular anaesthesia. With the exception of 2 subjects, in whom the referred pain continued in the absence of primary pain, the referred pain declined in parallel with local pain: the mean total pain intensity declined by 74% in both regions. We conclude that the maintenance of referred muscle pain usually depends on ongoing noxious inputs from the site of primary muscle pain. Referred pain is a significant clinical problem, and commonly occurs with pain originating in muscle but not from skin. It is important to know the primary source of the pain so that treatment can be directed to this site rather to the site of referral. What happens to the intensity of pain induced by repeated noxious stimuli over time? Does it stay the same, increase or decrease? In the second study we tested the hypothesis that the intensity and area of pain in the local and referred regions exhibits plasticity when an identical noxious stimulus is delivered to the same site over sequential trials. In this repeated measures study over 4 weeks we demonstrated a progressive reduction in the area and intensity of local pain and a reciprocal increase in the expression of referred pain. We conclude that the decrease in perceived local pain and increase in perceived referred pain reflects plastic processes occurring centrally. We show that weekly injections of hypertonic saline into tibialis anterior cause decreases in local but increases in referred pain, suggesting central changes in processing noxious inputs. While current data suggests that all referred pain derives from common mechanisms of central sensitisation, there is a paucity of data directly comparing referral in different limbs. Does a common mechanism result in similar precepts of referral from identical stimuli in different limbs? We tested the hypothesis that the incidence, intensity and spatiotemporal expression of referred pain are identical during the muscle pain induced by bolus intramuscular injection of hypertonic saline into flexor carpi radialis (FCR) and tibialis anterior (TA). We also tested the hypothesis that an increase in stimulus intensity causes a parallel increase in the incidence and intensity of local and referred pain, by comparing the responses to 5% and 10% hypertonic saline in two groups of subjects. 36 subjects mapped areas of local and referred pain, rating intensities on a visual analogue scale, every 30s until the cessation of pain. Local pain from injections of the 10% solution into either muscle was significantly higher than that produced by injection of the 5% solution. However, while the mean intensity of referred pain was consistently greater after the 10% injections, the increase was greater for FCR than for TA. Our observation that increasing concentrations can have dramatically different effects on referred pain suggest that local pain may be related to a saturation in the perception of local pain rather than a saturation of afferent barrage. Furthermore, the relationship between the perceptual saturation of local pain and the expression of referred pain may vary from muscle group to muscle group. It is well established that the insula cortex processes noxious information. We have previously shown that noxious inputs from the arm and leg are coarsely organized somatotopically within the dorsal posterior insula. The same has been shown for inputs from C tactile afferents, which mediate affective touch, and it has been suggested that the insula may be responsible for the localization of some somatosensory stimuli. Knowing the degree of spatial detail may have significant implications for the potential role of the dorsal posterior insula in the processing of noxious stimuli. Using high-resolution functional magnetic resonance imaging (fMRI) we compared insula activation patterns during muscle pain induced by injection of hypertonic saline into three muscles within the same limb: shoulder (deltoid), forearm (flexor carpi radialis) and hand (first dorsal interosseous). Mapping the maximally activated voxels within the contralateral dorsal posterior insula in each individual subject during each pain stimulus revealed a clear somatotopy of activation within the contralateral dorsal posterior insula. Shoulder pain was represented anterior to forearm pain and medial to hand pain. This fine somatotopic organization may be crucial for pain localization or other aspects of the pain experience that differ depending on stimulation site.

Date of Award	2010
Original language	English