Evidence Details for Htr1a
PMID Title Journal Year Abstract
29034548 Electroacupuncture alleviates chemotherapy-induced pain through inhibiting phosphorylation of spinal CaMKII in rats. Eur J Pain. 2018 Apr;22(4):679-690. doi: 10.1002/ejp.1132. Epub 2017 Oct 16. 2018 Apr BACKGROUND: Current medical treatments for chemotherapy-induced pain (CIP) are either ineffective or have adverse side effects. Acupuncture may alleviate CIP, but its effectiveness against this condition has not been studied. Paclitaxel causes neuropathic pain in cancer patients. METHODS: We evaluated the effects of electroacupuncture (EA) on paclitaxel-induced CIP in a rat model. Paclitaxel (2 mg/kg) or vehicle was injected (i.p.) on alternate days of 0-6. The resulting pain was treated with 10 Hz/2 mA/0.4 ms pulse EA for 30 min at the equivalent of human acupoint GB30 (Huantiao) once every other day between days 14 and 26. For sham control, EA needles were inserted into GB30 without stimulation. Von Frey filaments with bending forces of 2-8 g and 15 g were used to assess mechanical allodynia and hyperalgesia, respectively, on day 13 and once every other day between 14-26 days and then for 2-3 weeks after EA treatment. RESULTS: Compared to sham control, EA significantly alleviated paclitaxel-induced mechanical allodynia and hyperalgesia, as shown by less frequent withdrawal responses to the filaments. The alleviation of allodynia/hyperalgesia lasted up to 3 weeks after the EA treatment. EA significantly inhibited phosphorylation of Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) in the spinal cord. KN-93, a selective inhibitor of p-CaMKII, inhibited mechanical allodynia/hyperalgesia and p-CaMKII. 5-HT1A receptor antagonist blocked EA inhibition of allodynia/hyperalgesia and p-CaMKII. CONCLUSIONS: Electroacupuncture activates 5-HT 1A receptors in the spinal cord and inhibits p-CaMKII to alleviate both allodynia and hyperalgesia. The data support acupuncture/EA as a complementary therapy for CIP. SIGNIFICANCE: Electroacupuncture (EA) activates spinal 5-HT1A receptors to inhibit p-CaMKII to alleviate paclitaxel-induced pain. Acupuncture/EA may be used as a complementary therapy for CIP."

Evidence Sentence: To investigate the roles of 5-HT1A receptors in the effect of EA on paclitaxel-induced pain, rats were injected with paclitaxel and divided into four groups (n=7 per group): 1) WAY-100635 (12.5 nmol / 5 mul, a 5-HT 1A receptor antagonist) + EA, 2) WAY-100635 + sham, 3) saline + EA, and 4) saline + sham.
Evidence Sentence: EA activates 5-HT 1A receptors in the spinal cord and inhibits p-CaMKII to alleviate both allodynia and hyperalgesia.
Evidence Sentence: As aforementioned in introduction, it is not known whether 5-HT1A receptors are involved in EA inhibition of neuropathic pain.
Evidence Sentence: To investigate the roles of 5-HT1A receptors in the effect of EA on paclitaxel-induced pain, rats were injected with paclitaxel and divided into four groups (n=7 per group): 1) WAY-100635 (12.5 nmol / 5 mul, a 5-HT 1A receptor antagonist) + EA, 2) WAY-100635 + sham, 3) saline + EA, and 4) saline + sham.
Evidence Sentence: These results suggest that spinal 5-HT1A receptor activation was involved in EA-produced relief of CIP.
Evidence Sentence: This indicates that activation of 5-HT1A receptors in the spinal cord alleviated paclitaxel-induced mechanical allodynia and hyperalgesia.
Evidence Sentence: To investigate the EA effect on p-CaMKII, the spinal cord was removed from the four groups of rats at day 20 after finishing the behavioral test in 5-HT1A receptor experiment.
Evidence Sentence: 3.3 5-HT1A receptor agonist alleviated paclitaxel-induced mechanical allodynia and hyperalgesia
Evidence Sentence: In another two groups of rats (n=7 per group), a 5-HT1A receptor agonist, 8-OH-DPAT (15 mug /5 mul), or vehicle was i.t.
Evidence Sentence: However, the intrathecal pretreatment with a 5-HT 1A receptor antagonist WAY-100635 in EA-treated rats significantly increased the mechanical response frequencies compared to the vehicle pretreatment, demonstrating that WAY-100635 blocked EA inhibition of the mechanical allodynia and hyperalgesia.
Evidence Sentence: 5-HT1A receptor antagonist blocked EA inhibition of allodynia/hyperalgesia and p-CaMKII.
Evidence Sentence: 3.2 5-HT1A receptor antagonist blocked EA alleviation of paclitaxel-induced mechanical allodynia and hyperalgesia
Evidence Sentence: 3.4 EA inhibited phosphorylation of spinal CaMKII and 5-HT1A receptor antagonist prevented such EA inhibition
Evidence Sentence: Further, pretreatment of intrathecal 5-HT1A receptor antagonist (group 1) increased the p-CaMKII levels in EA-treated rats compared to the vehicle pretreatment (group 3).
Evidence Sentence: This demonstrates that 5-HT1A receptor antagonist blocked EA reduction of p-CaMKII levels and suggests that EA may inhibit phosphorylation of CaMKII through activation of 5-HT1A receptors in the spinal cord.