NOCICEPTIVE NEURONS IN AREA-24 OF RABBIT CINGULATE CORTEX

1. Single-unit responses in area 24 of cingulate cortex were examined in halothane-anesthetized rabbits during stimulation of the skin with transcutaneous electrical (TCES, 3-10 mA), mechanical (smooth or serrated forceps to the dorsal body surface or graded pressures of 100-1,500 g to the stabilized ear) and thermal (>25-degrees-C) stimulation. 2. Of 542 units tested in cingulate cortex, 150 responded to noxious TCES (greater-than-or-equal-to 6 mA), 93 of 221 units tested responded to noxious mechanical (serrated forceps) and 9 of 47 units tested responded to noxious heat (>43-degrees-C) stimuli. Twenty-five percent of the units that responded to noxious mechanical stimuli also responded to noxious heat stimuli. The only innocuous stimulus that evoked activity in cingulate cortex was a "tap" to the skin and this was effective for 11 of 14 tested units. 3. In 74 units that produced excitatory responses to TCES of the contralateral ear, response latency was 166 +/- 11.3 (SE) ms and response duration was 519 +/- 52.1 ms. 4. Twenty of the 150 units that responded to noxious TCES were initially inhibited. These responses were usually <1 s in duration (17 of 20 units), whereas responses in the other 3 lasted for over 20 s. 5. Most units had broad receptive fields, because noxious mechanical stimuli anywhere on the dorsal surface of the rabbits, including the face and ears, evoked responses. A small number of units for which the entire body surface was tested (3 of 15 units) had receptive fields limited to the ears, rostral back, and forepaws. 6. Fifteen of 33 units tested had no preferential responses to noxious TCES of the ipsilateral and contralateral ears. Of the remaining units, 10 had a greater response to contralateral and 8 had a greater response to ipsilateral stimuli. 7. The locations of 186 units were histologically verified. Most nociceptive cingulate units were in dorsal area 24b in layers III (n = 35), II (n = 13), or V (n = 9). 8. Cortical knifecut lesions were made in five rabbits to determine if the responses in area 24 were dependent on lateral or posterior cortical inputs. These lesions did not alter the percentage of units driven by noxious stimuli nor response latency. 9. Injections of lidocaine were made into medial parts of the thalamus in six animals and injection and recording sites analyzed histologically. The excitatory responses evoked in 12 cortical units with noxious stimuli were virtually eliminated with lidocaine injections that were in the parafascicular nucleus or as far rostral as the submedial nucleus. 10. The broad receptive fields and high thresholds of the area 24 neurons were similar to responses described previously in the medial and intralaminar thalamus in several species. Because area 24 receives substantial input from these thalamic nuclei and the cingulate cortical responses could be blocked with thalamic lidocaine injections, thalamic projections may mediate the cingulate responses to noxious stimuli. 11. The presence of nociceptive neurons in area 24b clarifies previous observations that area 24 1) is crucial for avoidance learning that employs noxious footshock as the unconditional stimulus, 2) has unit activity that is highly correlated with heart rate in classical conditioning paradigms, and 3) is a suitable neurosurgical target for the alleviation of pain in patients with chronic diseases.