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  4. Role of brainstem noradrenergic neurons in modulation of operant nocifensive responses to heat: Pharmacology and hyperalgesia.

Role of brainstem noradrenergic neurons in modulation of operant nocifensive responses to heat: Pharmacology and hyperalgesia.

Chatterjee K, Kline IV RH, Wiley RG (2009) Role of brainstem noradrenergic neurons in modulation of operant nocifensive responses to heat: Pharmacology and hyperalgesia. Neuroscience 2009 Abstracts 855.10/X15. Society for Neuroscience, Chicago, IL.

Summary: Many spinal dorsal horn neurons are under direct modulation from various brainstem nuclei which act to modulate nociceptive activity. Nocifensive reflex response modulation by spinally projecting noradrenergic brainstem nuclei has been extensively categorized. Strong evidence supports a role for these neurons in the modulation of reflex nocifensive responses but the role of noradrenergic neurons in the cerebral component of nociception remains to be defined in rats. In the present study, we sought to determine the effects of selectively destroying noradrenergic rostral brainstem neurons (A5,A6,A7) on operant escape from 44°C floor heat under several conditions: 1-baseline (after i.c.v. toxin/vehicle injection), 2- after s.c. injection of morphine, clonidine or yohimbine, 3- three hours after bilateral dorsal hindpaw application of mustard oil (secondary hyperalgesia), and 3- three hours after bilateral plantar application of 0.9% capsaicin cream (primary hyperalgesia). Rats were tested daily until steady operant escape responding (~1 month), then injected i.c.v. with 10µl of PBS (vehicle control, n=8) or antiDBH-saporin (10µg, n=8). After recovery from toxin injection, escape responses decreased in the antiDBH-sap rats. Morphine (0, 0.5, 1.0, 2.0 mg/kg s.c.) 20 min prior to testing, dose dependently attenuated escape from the noxious thermal plate at 44oC for all treatment groups. antiDBH-sap treated rats, however, showed an enhanced morphine effect (more prolonged occupancy of the noxious thermal plate). Three hours after plantar capsaicin, or mustard oil to the dorsal surface of both hindpaws, PBS but not antiDBH-sap rats showed enhanced escape. Systemic clonidine (0.125mg/kg) decreased escape for both PBS and antiDBH-sap treated rats, but the anti-nociceptive effect was greater in antiDBH-sap rats. Systemic yohimbine (1.0, 2.5, 5.0mg/kg) had no effect on escape in antiDBH-sap rats but enhanced escape in PBS rats. In direct contrast to effects on escape responding, antiDBH-sap did not affect hotplate lick/guard initial latencies to nociceptive heat at 44° or 47oC. Escape responses to aversively bright light were also decreased in antiDBH-sap rats suggesting generally decreased responsiveness to aversive stimuli. These results support a significant role for rostral brainstem noradrenergic neurons in modulation of pain and highlight important differences between reflex nocifensive responses (hotplate) and operant (escape) responses.

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