Inoculation of Lewis lung carcinoma cells enhances formalin-induced pain behavior and spinal Fos expression in mice.

The incidence of lung cancer has rapidly increased and cancer patients at a later cancer stage frequently suffer from unbearable cancer-associated pain. However, the pathophysiology of lung cancer pain has not been fully described due to a lack of appropriate animal models. This study was designed to determine the effect of Lewis lung carcinoma (LLC) cell inoculation on formalin-induced pain behavior and spinal Fos expression in C57BL/6 mice. LLC cells (1.5 × 105, 2.5 × 105, 3.0 × 105 or 5.0 × 105) were inoculated into back or peri-sciatic nerve areas. Back area inoculation was adopted to determine the effect of cancer cell circulating factors and the peri-sciatic nerve area was used to evaluate the possible effects of cancer cell contacting and circulating factors on formalin-induced pain. At postinoculation day 7, LLC cell (5.0 × 105) inoculations in both back and peri-sciatic nerve area significantly increased formalin-induced paw-licking time and spinal Fos expression over those in cell-media-inoculated (control) mice. Enhanced pain behavior and spinal Fos expression were significantly suppressed by ibuprofen pretreatment (250 mg/kg). The results of this study suggest that LLC cell circulating factors and inflammatory responses may be critical in enhancing pain sensation in the early stage of lung cancer cell inoculation.

Analgesic effect of electroacupuncture on paclitaxel-induced neuropathic pain via spinal opioidergic and adrenergic mechanisms in mice.

This study was designed to determine the antinociceptive effect and related neuronal mechanism of electroacupuncture (EA) on paclitaxel (PTX)-induced neuropathic pain in mice. PTX (4 mg/kg, i.p.) was administered once a day for 5 consecutive days to induce neuropathic pain. EA stimulation (2 mA, 2 Hz, 30 min) was applied at the ST36 acupoint bilaterally once in every 2 days. Repeated EA stimulation significantly attenuated PTX-induced mechanical allodynia and thermal hyperalgesia. In a separate set of experiment, the antinociceptive effect of a single EA stimulation 8 days after PTX treatment was reduced by intrathecal pretreatment with naloxone (opioid receptor antagonist), idazoxan (alpha2-adrenoceptor antagonist) or propranolol (beta-adrenoceptor antagonist), but not prazosin (alpha1-adrenoceptor antagonist). Moreover, EA remarkably suppressed the PTX-enhanced phosphorylation of the NMDA receptor NR2B subunit in the spinal dorsal horn, and intrathecal pretreatment of naloxone, idazoxan (IDA) or propranolol blocked the effect of EA. In conclusion, EA stimulation at the ST36 acupoint significantly diminished PTX-induced neuropathic pain in mice via the mediation of spinal opioid receptor, alpha2- and beta-adrenoceptors.