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Lower limb pain is a common clinical disease that affects millions of people worldwide. It is found in previous studies that reactive oxygen species is closely related to neuropathic, cancer, chemotherapy, and inflammatory pain, which can be relieved by reactive oxygen species scavengers. Furthermore, acupuncture or electroacupuncture on the psoas major muscle has a great effect on adjuvant-induced arthritis and lower back pain. In our study, we investigated the function of reactive oxygen species scavengers locally injecting into the ipsilateral psoas major muscle on complete Freund's adjuvant-induced inflammatory pain. Our results demonstrated that in the development of complete Freund's adjuvant-induced inflammatory pain, early local continuous application of N-tert-Butyl-α-phenylnitrone (PBN, 1 and 5 mg/kg/0.2 ml) on the ipsilateral psoas major muscle effectively reduced mechanical and cold hyperalgesia. However, intraperitoneal injection of PBN (1 and 5 mg/kg) or local injection of PBN (1 and 5 mg/kg/0.2 ml) into contralateral psoas major muscle, ipsilateral quadratus lumborum, and ipsilateral erector spinae showed limited effect. In the developed inflammatory pain model, local injection of PBN into the ipsilateral psoas major muscle also alleviated pain and paw edema. In addition, reactive oxygen species level increased in ipsilateral psoas major muscle at seven days after complete Freund's adjuvant injection. In general, PBN reduces complete Freund's adjuvant-evoked inflammatory pain by inhibiting reactive oxygen species in the psoas major muscle.

Transient receptor potential ankyrin subfamily member 1 (TRPA1) is a nonselective cation channel known as a noxious cold-activated ion channel. Recent findings implicated its involvement in acute and chronic cold nociception processes. Here, we investigated whether TRPA1 is involved in endothelin-1 (ET-1)-induced spontaneous pain-like behavior in C57BL/6J mice. We found that TRPA1 antagonists, HC-030031 and AP18, significantly reduced the pain-like behavior caused by ET-1. AP18 also significantly reduced the pain caused by cinnamaldehyde, an agonist of TRPA-1. However, AP18 did not alleviate the pain caused by capsaicin. The pain-like behavior caused by ET-1 was inhibited by phospholipase C inhibitor, but not by protein kinase C inhibitor. Low dose of ET-1 could potentiate cinnamaldehyde-induced nociception. Our results suggested that TRPA1 is involved in ET-1-induced spontaneous pain-like behavior in mice.

Although local administration of endothelin-1 (ET-1) is known to evoke spontaneous pain, the mechanism of ET-1-induced pain has not been elucidated. We investigated the involvement of protein kinase C (PKC) and transient receptor potential vanilloid subfamily 1 (TRPV1) in ET-1-induced pain-like behavior. Intraplantar ET-1 evoked pain-like behaviors, including licking, flinching, and biting, in a dose-dependent manner in wild-type mice. ET-1-induced pain-like behavior was attenuated by an endothelin type A receptor antagonist but not by PKC inhibitors and was also attenuated in TRPV1-deficient (KO) mice. In addition, we found a significant reduction of spinal Fos expression caused by the same dose of ET-1 in KO mice compared with that in wild-type mice. This study showed that endothelin type A receptor and TRPV1 are involved in ET-1-induced pain-like behaviors but failed to reveal the contribution of PKC.

Objective. Recently, evidence has accumulated to show that cation-chloride cotransporters (CCCs) participate in the modulation of pain transmission at the spinal cord level. To investigate whether CCC inhibitors might affect surgical pain, we examined the effect of furosemide in a rat incisional pain model. Design. We examined pain thresholds using von Frey filaments in intact and incision model Sprague-Dawley rats before and after intrathecal furosemide administration (100 µg/20 µL). Twenty-four rats were divided into four groups (N = 6), groups A and B were intact rats, which received furosemide and its solvent, respectively. Groups C and D were incision rats, which received furosemide and its solvent, respectively. Non-parametric tests were used to calculate pain thresholds, and P < 0.05 was considered significant. Results. Furosemide decreased the pain threshold (vs solvent) in intact rats for 2 hours after administration and caused excitatory behavior. However, furosemide increased the pain threshold in incision model rats ([1] at the incision point: at 20 minutes, 2 hours, 3 hours, 4 hours, and on the second to fifth days after incision; [2] at the remote point: at 20 minutes, 3-5 hours, and from the 3rd to the 7th day after incision) and improved wound recovery. Conclusions. Intrathecal administration of the CCC inhibitor furosemide had antinociceptive effects in rats with incisional pain. Furosemide may be a novel treatment for postoperative pain. [ABSTRACT FROM AUTHOR]