The efficacy of 5 alpha-androstane-3 alpha,17 beta-diol 3 alpha-Andros
tanediol; 3 alpha-Diol) and 4-pregnen-3,20-dione (progesterone; P) in
promoting analgesia was investigated. Ovariectomized rats received dai
ly injections of 3 alpha-Diol (0.6, 3.0, 6.0 and 7.5 mg/kg) or vehicle
and twice daily injections of estradiol-17 beta (E(2): 1 mu g) for 2
days. Progesterone (0.5, 1.0, 2.0 and 4.0 mg/kg) or its vehicle was gi
ven on the third day and nociceptive testing using the radiant heat ta
ilflick method was carried out 4 h later. In Expt. 1, P and 3 alpha-Di
ol both produced analgesia and had biphasic dose-response effects when
administered singly. 3 alpha-Diol (3.0 mg/kg) elevated tailflick late
ncies in E(2)-primed animals above those following vehicle, 6.0 or 7.5
mg/kg 3 alpha-Diol; 6.0 and 7.5 mg/kg produced elevations that were g
reater than vehicle but less than 3.0 mg/kg. Progesterone (0.5 and 1.0
mg/kg) also elevated tailflick latencies above vehicle controls, whil
e 2.0 and 4.0 mg/kg produced intermediate effects. In Expt. 2, 3 alpha
-Diol (3 alpha-Diol:BSA) and P (P:BSA) conjugated to bovine serum albu
min (BSA) were applied to the medial basal hypothalamus (MBH) and preo
ptic area (POA) to ascertain whether the steroids' analgesic actions w
ere mediated by membrane actions in these sites. Free P and P:BSA both
increased tailflick latencies when applied to the MBH, while 3 alpha-
Diol and 3(alpha-Diol:BSA elevated latencies when applied to the POA,
suggesting the steroids' effects occur in part at the neuronal membran
e. In Expt. 3, free P or P:BSA applied to the MBH did not increase tai
lflick latencies if systemic P was given concurrently. Similarly, free
3 alpha-Diol and 3 alpha-Diol:BSA implants into the POA failed to inc
rease tailflick latencies if s.c. 3 alpha-Diol was co-administered. Th
ese data indicate that P and 3 alpha-Diol at moderate doses have analg
esic effects in part via membrane actions within the MBH and POA, resp
ectively.