OBJECTIVE To explore the role of histamine in acute pain perception.METHODS We studied the sensitivity to acute pain in histidine decarboxylase knockout mice(HDC-/-),wild-type mice treated with α-fluoromethylhistidine(α-FMH),a specific HDC inhibitor,and mice feed a low-histamine diet.Morphological,Western blotting and Electrophysiology studies were taken to explore the involvement of sodium channel 1.8(Nav 1.8) in the pathological process.RESULTS Behavioral tests revealed that HDC-/-mice had lower nociceptive thresholds for acute thermal(hot-plate),mechanical(tail-pressure) and chemical(acetic acid and formalin) stimulation than the wild-type.The low-histamine diet elevated the sensitivity to all these noxious stimuli in the wild-type,and to heat and formalin stimuli in the HDC-/-mice.α-FMH treatment also augmented acute thermal nociception in the wild-type.Morphological and Western blotting studies showed that both HDC knockout and α-FMH treatment increased the expression of Nav1.8 in nociceptive primary afferent neurons.The higher Nav1.8 current density in nociception-related small DRG neurons of HDC-/-mice verified this upregulation.Moreover,the current required to evoke action potentials was significantly lower,and the firing rate in response to suprathreshold stimulation was higher in neurons from HDC-/-mice.The hyperexcitability of DRG neurons in HDC-/-mice was diminished by a Nav1.8 inhibitor,but not TTX.CONCLUSION Our results indicate that histamine participates in acute pain modulation,which may be related to the regulation of Nav1.8 in,as well as the excitability of,nociceptive primary afferent neurons. OBJECTIVE To explore the role of histamine in acute pain perception. METHODS We studied the sensitivity to acute pain in histidine decarboxylase knockout mice (HDC - / -), wild-type mice treated with α-fluoromethylhistidine (α-FMH), a specific HDC inhibitor, and mice feed a low-histamine diet. Morphological, Western blotting and Electrophysiology studies were taken to explore the involvement of sodium channel 1.8 (Nav 1.8) in the pathological process. RESULTS Behavioral tests revealed that HDC - / - mice had lower nociceptive thresholds for acute thermal (hot-plate), mechanical (tail-pressure) and chemical (acetic acid and formalin) stimulation than the wild-type. The low-histamine diet elevated the sensitivity to all these noxious stimuli in the wild- and to heat and formalin stimuli in the HDC - / - mice. α-FMH treatment also augmented acute thermal nociception in the wild-type. Morphological and Western blotting studies showed that both both HDC knockout and α-FMH treatment increased the expression of Nav1. 8 in nociceptive primary afferent neurons. The higher Nav1.8 current density in nociception-related small DRG neurons of HDC - / - mice verified this upregulation. More over, the current required to evoke action potentials was significantly lower, and the firing rate in response to suprathreshold stimulation was higher in neurons from HDC - / - mice. hyperexcitability of DRG neurons in HDC - / - mice was diminished by a Nav1.8 inhibitor, but not TTX. CONCLUSION Our results indicate that histamine participates in acute pain modulation, which may be related to the regulation of Nav1.8 in, as well as the excitability of, nociceptive primary afferent neurons.