Effects of systemic bicuculline or morphine on formalin-evoked pain-related behaviour and c-Fos expression in trigeminal nuclei after formalin injection into the lip or tongue in rats

This study examined differences in nociceptive responses between lip and tongue. Formalin-induced pain-related behaviour and c-Fos expression in the trigeminal caudal nucleus (Vc) with/without systemic preadministration of a γ-aminobutyric acid (GABA) type A receptor antagonist, bicuculline (2 mg/kg, i.p., 10 min before formalin injection) or a μ-opioid receptor agonist, morphine (3 mg/kg, i.p., 10 min before formalin injection) have been studied. Formalin injection into the upper lip induced an immediate pain-related behaviour, mostly face-rubbing behaviour, for 15 min (phase 1, mean ± SEM/5 min, 81.2 ± 30.1), followed by a more increased activity for 15 min (phase 2, 205.4 ± 43.6) and a decline to baseline for next 15 min (phase 3, 63.9 ± 28.0). Formalin injection into the tongue induced similar amount of pain-related behaviour at phase 1 (67.9 ± 16.7), followed by similar activity at phase 2 (48.6 ± 6.2), and lesser behaviour at phase 3 (20.4 ± 7.6). The behaviour at phase 2 decreased following preadministration of bicuculline or morphine when formalin was injected into the lip (b, 62.5 ± 14.5; m, 95.8 ± 10.0) but not into the tongue (b, 31.0 ± 9.2; m, 77.4 ± 27.0). A considerable numbers of c-Fos-immunoreactive (IR) cells were induced in the caudal and inter-medio-lateral center of superficial layers of the Vc (VcI/II; mean ± SEM/section = 225.8 ± 12.9) and magnocellular zone of the Vc (VcIII/IV; 67.1 ± 4.7) 2 h after formalin injection into the lip. Much smaller numbers of c-Fos-IR cells were induced in the rostral and dorso-medial one-fourth of the VcI/II (72.6 ± 3.7) and VcIII/IV (55.6 ± 6.6) after formalin injection into the tongue. Following preadministration with systemic bicuculline or morphine, the formalin-induced c-Fos-IR cells were decreased more in the VcI/II when formalin was injected into the lip (VcI/II, 102.4 ± 8.0; VcIII/IV, 32.8 ± 1.4) than into the tongue (VcI/II, 49.5 ± 8.1; VcIII/IV, 31.7 ± 5.3). These results show that the lip is more sensitive to formalin-induced noxious stimulation and regulated more through GABA_A and μ-opioid receptors than the tongue.