To investigate the effect of dexmedetomidine on inflammatory mediators of substance P (SP), calcitonin gene related peptide (CGRP), serum tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and IL-6 in mice with formaldehyde-induced pain.

Forty male C57 mice were divided into a control group, a low dose group, a medium dose group and a high dose group, 10 in each group. Mice in the low, medium and high dose groups were given intraperitoneal injection of 10, 20, and 30 μg/kg dexmedetomidine respectively, while mice in the control group were given intraperitoneal injection of 10 mL/kg isosmotic NaCl solution. Thirty minutes later, 20 μL of 2% formaldehyde was subcutaneously injected into the right foot of mice under isoflurane anesthesia, and the licking time was recorded in each group. The expression levels of SP and CGRP in the spinal cord and ganglion were observed by immunofluorescence staining. The expression levels of SP, CGRP in the spinal cord and ganglion supernatant and TNF-α, IL-1β, IL-6 in serum were determined by enzyme-linked immunosorbent assay (ELISA).

After the plantar injection of formaldehyde, the licking time was (12.9 ± 5.0) s in the control group, (8.4 ± 3.1) s in the low dose group, (7.9 ± 2.7) s in the medium dose group, and (7.8 ± 2.5) s in the high dose group. It was significantly different among these four groups (F = 19.472, P = 0.018), and mice had significantly prolonged licking time in the control group than in the other three groups (all P < 0.05). Immunofluorescence staining showed that the SP expression level at the dorsal horn of spinal cord and nodular ganglia was higher in the control group than in the other three groups, with bright green fluorescent fibers, and that it was minimal in the high dose group. In the meantime, the CGRP expression level at the dorsal horn of spinal cord and nodular ganglia was low in each group, and no red positive fibers and neuronal cell bodies were obviously found. ELISA showed that the expression levels of SP at the dorsal horn of spinal cord [(43 ± 9), (33 ± 7), (31 ± 7), (20 ± 5) ng/L], SP at nodular ganglia [(30 ± 7), (20 ± 5), (22 ± 5), (13 ± 3) ng/L], TNF-α [(381 ± 60), (340 ± 54), (330 ± 48), (289 ± 41) ng/L], IL-1β [(68 ± 19), (55 ± 16), (52 ± 16), (41 ± 13) ng/L], and IL-6 [(55 ± 15), (53 ± 15), (45 ± 11), (39 ± 10) ng/L] were statistically different among the control group, low dose group, medium dose group and high dose group (F = 6.527, 5.269, 35.612, 33.843, 37.175; P = 0.031, 0.022, 0.036, 0.048, 0.029). In further pairwise comparison, the expression levels of SP at the dorsal horn of spinal cord and nodular ganglia, TNF-α and IL-1β in the low, medium and high dose groups, and IL-6 in the medium and high dose groups were significantly lower than those in the control group, and those were lowest in the high dose group (all P < 0.05).

The neuropeptide SP at the dorsal horn of spinal cord and nodular ganglia may be involved in the release of pain-related inflammatory mediators, while dexmedetomidine inhibits their expressions and reduces levels of inflammatory factors in serum.