The focus of this project is to determine the basic neural mechanisms that mediate muscle pain and deep hyperalgesia.
The specific aims are to compare psychophysical measures of muscle pain and hyperalgesia in humans to evoked responses of single human muscle afferents and spinal dorsalhorn neurons recorded in anesthetized monkeys, using similar stimuli. Muscle pain will be produced by intramuscular injection of the irritant capsaicin, and by direct intraneural electrical stimulation. Following injection of capsaicin (0.01-100 mg) into the gastrocnemius- soleus muscle, in humans, the quality, magnitude and duration of spontaneous pain and hyperalgesia to gentle pressure of these muscle will be assessed. These results will provide information about the capacity of humans to scale the magnitude of deep pain. In electrophysiological studies in humans, single nociceptive muscle afferents from the common peroneal nerve will be identified, and stimulus-response characteristics determined through combined intraneural stimulation and recording. Capsaicin will be injected into their receptive field and estimates of pain magnitude and evoked afferent activity will be recorded simultaneously. Judgments of pain induced by pressure will be compared to simultaneously evoked responses before and after injection. In additional studies, trains of electrical stimuli will be delivered intraneurally at different frequencies. Subjects will map the area of deep projected pain and estimate the magnitude of evoked pain. This will give information regarding encoding properties of human muscle nociceptors. In anesthetized monkeys,recordings will be made from spinothalamic tract (STT) cells with receptive fields innervating the gastrocnemius-soleus muscle. Receptive field area, spontaneous activity and responses to quantitative mechanical stimulation of muscle will be obtained before and after intramuscular injections of vehicle and capsaicin. Discharges of STT cells evoked by capsaicin and by mechanical stimuli will be compared to the magnitude of pain and mechanical hyperalgesia in humans produced by identical stimuli. These studies will be the first to determine stimulus-response characteristics of human muscle nociceptors and to compare their activity and activity of spinal neurons, with psychophysical measures of muscle pain. Results will provide new knowledge concerning neural mechanisms of muscle pain, as well as insight into pathophysiology of muscle pain syndromes associated with injury or disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29NS031223-01
Application #
3478631
Study Section
Sensory Disorders and Language Study Section (CMS)
Project Start
1993-02-01
Project End
1998-01-31
Budget Start
1993-02-01
Budget End
1994-01-31
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Khalili, N; Wendelschafer-Crabb, G; Kennedy, W R et al. (2001) Influence of thermode size for detecting heat pain dysfunction in a capsaicin model of epidermal nerve fiber loss. Pain 91:241-50
Nolano, M; Simone, D A; Wendelschafer-Crabb, G et al. (1999) Topical capsaicin in humans: parallel loss of epidermal nerve fibers and pain sensation. Pain 81:135-45
Li, J; Simone, D A; Larson, A A (1999) Windup leads to characteristics of central sensitization. Pain 79:75-82
Allen, B J; Li, J; Menning, P M et al. (1999) Primary afferent fibers that contribute to increased substance P receptor internalization in the spinal cord after injury. J Neurophysiol 81:1379-90
Li, J; Daughters, R S; Bullis, C et al. (1999) The cannabinoid receptor agonist WIN 55,212-2 mesylate blocks the development of hyperalgesia produced by capsaicin in rats. Pain 81:25-33
Simone, D A; Nolano, M; Johnson, T et al. (1998) Intradermal injection of capsaicin in humans produces degeneration and subsequent reinnervation of epidermal nerve fibers: correlation with sensory function. J Neurosci 18:8947-59
Mantyh, P W; Rogers, S D; Honore, P et al. (1997) Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor. Science 278:275-9
Simone, D A; Kajander, K C (1997) Responses of cutaneous A-fiber nociceptors to noxious cold. J Neurophysiol 77:2049-60
Marchettini, P; Simone, D A; Caputi, G et al. (1996) Pain from excitation of identified muscle nociceptors in humans. Brain Res 740:109-16
Gilchrist, H D; Allard, B L; Simone, D A (1996) Enhanced withdrawal responses to heat and mechanical stimuli following intraplantar injection of capsaicin in rats. Pain 67:179-88

Showing the most recent 10 out of 11 publications