Fig. 6. Inhibition of sympathetic outflow prevents stress-induced hyperalgesia in α-2A knockout (KO) mice. (A –C ) Paw withdrawal latencies after no stress (red bars ) or ultrasonic stress (blue bars ) in wild-type (WT) and α-2A KO mice after pretreatment with a saline control (n = 6) or the α-1 receptor antagonist prazosin, by (A ) intraperitoneal (IP, 0.1 μg/kg−1; n = 6) or (B ) intrathecal (10 ng; n = 6) injection, or (C ) after guanethidine (guan) sympathectomy (n = 8, except n = 10 in guanethidine-treated KO group). (D ) Tactile pain scores (n = 6, except n = 5 in 100, 300, 3,000 ng/kg−1KO groups) and (E ) paw withdrawal latencies (n = 6, except n = 4 in 100 ng/kg−1KO group and n = 7 in 3,000 ng/kg−1KO groups) in response to IP sulprostone in WT and α-2A KO mice with guanethidine sympathectomy (green, WT; light blue, KO) compared with data without guanethidine sympathectomy from figures 4 A and B (red, WT; blue, KO). Intraperitoneal prazosin and guanethidine sympathectomy prevent hyperalgesia in response to stress and sulprostone in α-2A KO mice. **=P < 0.01; ***=P < 0.001, increase in latency versus no stress (analgesia); §=P < 0.001, increase in pain score versus no sulprostone (allodynia); +=P < 0.05; ++=P < 0.01; +++=P < 0.001, decrease in latency versus no stress or versus no sulprostone (hyperalgesia). Data are expressed as mean ± SEM.