SPINAL NOCICEPTIVE TRANSMISSION IN THE SPONTANEOUSLY HYPERTENSIVE ANDWISTAR-KYOTO NORMOTENSIVE RAT

Background and noxious heat-evoked responses of wide-dynamic-range (WD R) and high-threshold (HT) lumbosacral spinal dorsal horn neurons were recorded in spontaneously hypertensive rats (SHRs), Wistar-Kyoto norm otensive rats (WKYs), lifetime captopril-treated SHRs, SHRs with bilat eral cervical vagotomy, SHRs with bilateral sino-aortic deafferentatio n (SAD), and SHRs with either a single or repeated administration of n aloxone methobromide (NMB). Stimulus-response functions (SRFs) were ge nerated for neurons using 15 sec of heating of the foot at temperature s ranging from 38 to 52 degrees C. Comparisons were made of neuronal r esponse thresholds, slopes of the SRFs, mean discharge frequency durin g heat stimulation, arterial blood pressure (ABP), and heart rate (HR) . The primary finding was that group mean SRFs for both WDR and HT neu rons were shifted in a parallel, rightward fashion in SHRs compared to WKYs. Heat-evoked response thresholds were increased and asymptotic d ischarge frequencies were decreased in WDR and HT neurons of SHRs comp ared to WKYs. Analyses of group mean SRFs for WDR and HT neurons of SH Rs receiving lifetime captopril treatment indicated they were normaliz ed to the SRFs of WKYs, but detailed comparisons using discharge frequ ency during heat stimulation revealed that this was due to a statistic al 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 heat ing compared to WKYs. Bilateral SAD in SHRs significantly increased th e 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 c ervical 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-administrat ion of a single dose of NMB did not differ. However, repeated administ ration of NMB in SHRs resulted in a parallel, leftward shift in SRFs o f both WDR and HT neurons. In all strains and treatments studied, ther e were no significant differences in background activities of these ne urons that might contribute to the observed outcomes. In conclusion, t he hypoalgesia reported in human essential hypertensives and animals w ith chronic hypertension may be due to a significant attenuation in sp inal nociceptive transmission. Our data are not definitive on whether increased ABP produced the attenuation of spinal nociceptive transmiss ion in SHRs because the use of the lifetime captopril treatment to low er systemic ABP of SHRs to levels of WKYs may also have affected endog enous facilitatory and inhibitory opioid systems. However, it was poss ible to demonstrate an inhibitory influence of both sine-aortic affere nts and endogenous central opioids on spinal nociceptive transmission in the SHR.