Spinal nociceptive transmission in the spontaneously hypertensive and Wistar-Kyoto normotensive rat.
Background and noxious heat-evoked responses of wide-dynamic-range (WDR) and high-threshold (HT) lumbosacral spinal dorsal horn neurons were recorded in spontaneously hypertensive rats (SHRs), Wistar-Kyoto normotensive rats (WKYs), lifetime captopril-treated SHRs, SHRs with bilateral cervical vagotomy, SHRs with bilateral sino-aortic deafferentation (SAD), and SHRs with either a single or repeated administration of naloxone methobromide (NMB). Stimulus-response functions (SRFs) were generated for neurons using 15 sec of heating of the foot at temperatures ranging from 38 to 52 degrees C. Comparisons were made of neuronal response thresholds, slopes of the SRFs, mean discharge frequency during heat stimulation, arterial blood pressure (ABP), and heart rate (HR). The primary finding was that group mean SRFs for both WDR and HT neurons were shifted in a parallel, rightward fashion in SHRs compared to WKYs. Heat-evoked response thresholds were increased and asymptotic discharge frequencies were decreased in WDR and HT neurons of SHRs compared to WKYs. Analyses of group mean SRFs for WDR and HT neurons of SHRs receiving lifetime captopril treatment indicated they were normalized to the SRFs of WKYs, but detailed comparisons using discharge frequency during heat stimulation revealed that this was due to a statistical averaging effect. Specifically, lifetime captopril-treated SHRs not only showed enhanced neuronal responses to the onset of noxious heat but also enhanced adaptation of neuronal responses with continued heating compared to WKYs. Bilateral SAD in SHRs significantly increased the total discharge frequency of WDR neurons to heat stimuli between 44 and 52 degrees C, but produced no change in the response threshold for heat-evoked activation of these neurons. A similar effect of SAD was observed in HT neurons of SHRs, but the greater response thresholds of HT neurons precluded detection of any significant effect. Bilateral cervical vagotomy did not affect response thresholds, slopes, or total discharge frequencies of SHRs, although only WDR neurons were studied. SRFs of WDR and HT neurons in SHRs obtained pre- and post-administration of a single dose of NMB did not differ. However, repeated administration of NMB in SHRs resulted in a parallel, leftward shift in SRFs of both WDR and HT neurons. In all strains and treatments studied, there were no significant differences in background activities of these neurons that might contribute to the observed outcomes. In conclusion, the hypoalgesia reported in human essential hypertensives and animals with chronic hypertension may be due to a significant attenuation in spinal nociceptive transmission.(ABSTRACT TRUNCATED AT 400 WORDS)
Randich
Alan
A
Department of Psychology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Robertson
Joel D
JD
D000818:Animals; D002216:Captopril / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006358:Hot Temperature; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008839:Microelectrodes; D009121:Muscle Denervation; D009270:Naloxone / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013238:Stereotaxic Techniques; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014628:Vagotomy
D009270:Naloxone; D002216:Captopril