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Biomedical subjects

Robert C Coghill

Publications and source records attributed to Robert C Coghill.

3 recordsLinked to original sources

Unilateral decrease in thalamic activity observed with positron emission tomography in patients with chronic neuropathic pain.

The oxygen-15 water bolus positron emission tomography (PET) method was used to image regional brain activity in 4 patients with chronic post-traumatic neuropathic pain confined to one lower limb and in 1 patient with post-herpetic neuralgia. In comparison to 13 normal subjects, scans of the patients disclosed a statistically significant decrease in thalamic activity contralateral to the symptomatic side. Examination of the right/left ratio for all the subjects showed that the values for the patients fell at the extremes of the normal range, according to the side of the affected body part. These initial observations suggest that functional alterations in thalamic pain processing circuits may be an important component of chronic neuropathic pain.

Adult

The roles of spatial recruitment and discharge frequency in spinal cord coding of pain: a combined electrophysiological and imaging investigation.

An investigation was conducted to examine both temporal and spatial factors likely to be involved in spinal cord nociceptive coding by wide cord nociceptive neurons. Three separate methodologies were employed. First, the impulse frequency responses of L4 spinal cord wide-dynamic-range (WDR) neurons to gentle mechanical stimulation, vigorous but innocuous brushing, warmth (43 degrees C), and nociceptive thermal stimuli (45-49 degrees C) were electrophysiologically characterized in unanesthetized, spinal cord-transected rats. Second, the spatial distribution of evoked activity in response to the same types of mechanical and thermal stimuli was examined utilizing the 14C-2-deoxyglucose (2-DG) metabolic mapping method in the same type of animal preparation. Finally, the contributions of impulse frequency and numbers of neurons activated to encoding the distinction between painful and non-painful sensations were directly evaluated by electrically stimulating axons within the spinal cord anterolateral quadrant (ALQ) of conscious human subjects. Electrophysiological findings revealed that vigorous but innocuous brushing produced intermediate rates of impulse discharge significantly greater than those produced by 35 and 43 degrees C stimuli, yet indistinguishable from those produced by relatively low nociceptive temperatures (45-47 degrees C). Thus, the discharge frequencies of individual dorsal horn WDR neurons alone do not provide sufficient information to encode the distinction between innocuous and low intensity nociceptive stimuli. Mapping of spinal cord activity by the 2-DG method revealed that nociceptive stimuli activated extensive rostro-caudal regions extending from L1-L5. In contrast, vigorous but innocuous brushing evoked metabolic activity that was confined to a narrow zone within L3. Thus, as predicted from previous studies, the distinction between nociceptive and non-nociceptive sensory events may be encoded, in part, by differences in the spatial distribution, and hence, the relative numbers of spinal cord neurons activated by nociceptive and innocuous stimuli. The responses of conscious human subjects to varying frequencies and intensities of electrical ALQ stimulation clarify the significance of the large numbers of spinal cord neurons activated by nociceptive stimuli. With stimulus frequency held constant at 50 Hz, low stimulus currents, sufficient to activate only small numbers of ALQ axons, produced innocuous sensations. Higher stimulus currents, sufficient to activate larger numbers of neurons, consistently produced painful sensations. Increasing ALQ stimulus frequency at currents subthreshold for pain or increasing stimulus currents at frequencies subthreshold for pain resulted in painful sensations, thus indicating that both discharge frequency and numbers of neurons activated are both important factors in the encoding of pain.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Spatial patterns of spinal cord [14C]-2-deoxyglucose metabolic activity in a rat model of painful peripheral mononeuropathy.

Spatial patterns of spinal cord glucose metabolic activity were examined in unanesthetized rats with painful peripheral mononeuropathy produced by sciatic nerve ligation (chronic constrictive injury, CCI). Spinal cord metabolic activity was assessed 10 days after nerve ligation by using the fully quantitative [14C]2-deoxyglucose technique. This technique allows simultaneous examination of both neural activity inferred from local glucose utilization and its spatial distribution in multiple spinal regions previously implicated in nociceptive processing. Rats used in the experiment exhibited thermal hyperalgesia to radiant heat applied to the hind paw ipsilateral to nerve ligation and behaviors indicative of spontaneous pain. Sciatic nerve ligation produced a significant increase in spinal cord metabolic activity in four sampling regions (laminae I-IV, V-VI, VII and VIII-IX) of lumbar segments compared to sham-operated rats. The pattern of altered metabolic activity in CCI rats presented 3 distinct features. (1) The spinal cord grey matter both ipsilateral and contralateral to nerve ligation exhibited substantial increases in metabolic activity compared to sham-operated rats. (2) This increase in metabolic activity was somatotopically specific, i.e., higher metabolic rates were observed on the side ipsilateral to nerve ligation than on the contralateral side, and higher metabolic rates were seen in the medial portion of the ipsilateral spinal cord dorsal horn than in the lateral portion. The peak metabolic activity occurred in laminae V-VI of CCI rats, a region involved in nociceptive processing. (3) The increase in spinal cord metabolic activity of CCI rats extended from lumbar segment L1 to L5 in all 4 sampling regions. The substantial increase in metabolic activity in both the ipsilateral and contralateral spinal cord that occurs over an extensive rostro-caudal area in CCI rats may represent a unique pattern of spinal cord metabolic activity distinct from that observed in rats exposed to acute thermal pain. This pattern of spinal cord neural activity in CCI rats may reflect possible radiation of neuropathic pain. In addition, the procedure of curare-induced paralysis in a separate group of CCI rats did not change the extent and patterns of metabolic activity seen in non-paralyzed CCI rats, reflecting a minimal influence of the afferent feedback from flexor motor reflexes on spinal cord metabolic activity following sciatic nerve ligation. This chronic increase in spinal cord neural activity in the absence of overt peripheral stimulation suggests a spinal cord hyperactive state and may account for behaviors suggestive of spontaneous pain in CCI rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals