Evidence Details for Camk2a
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: EA significantly inhibited phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the spinal cord.
Evidence Sentence: Electroacupuncture alleviates chemotherapy-induced pain through inhibiting phosphorylation of spinal CaMKII in rats
Evidence Sentence: EA significantly inhibited phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the spinal cord.
Evidence Sentence: KN-93, a selective inhibitor of p-CaMKII, inhibited mechanical allodynia/hyperalgesia and p-CaMKII.
Evidence Sentence: 5-HT1A receptor antagonist blocked EA inhibition of allodynia/hyperalgesia and p-CaMKII.
Evidence Sentence: EA activates 5-HT 1A receptors in the spinal cord and inhibits p-CaMKII to alleviate both allodynia and hyperalgesia.
Evidence Sentence: 3.4 EA inhibited phosphorylation of spinal CaMKII and 5-HT1A receptor antagonist prevented such EA inhibition
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: 4) showed significantly higher levels of p-CaMKII than vehicle-injected rats with i.t.
Evidence Sentence: saline and sham EA (group 5), indicating higher p-CaMKII levels in the spinal cord during CIP.
Evidence Sentence: EA treatment in paclitaxel-injected rats (group 3) significantly decreased p-CaMKII levels compared to sham (group 4), suggesting that EA treatment inhibited the phosphorylation of CaMKII in the spinal cord.
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.
Evidence Sentence: 3.5 CaMKII phosphorylation inhibitor inhibited paclitaxel-induced mechanical allodynia and hyperalgesia
Evidence Sentence: Since EA inhibited phosphorylation of spinal CaMKII, it is necessary to investigate whether the spinal p-CaMKII is involved in the CIP.
Evidence Sentence: We tested the effects of a selective CaMKII phosphorylation inhibitor, KN-93, and its inactive analog, KN-92, on mechanical allodynia and hyperalgesia in two groups of rats (n=7 per group).
Evidence Sentence: This indicates that KN-93 may inhibit pain through suppressing the p-CaMKII.
Evidence Sentence: 3.6 CaMKII phosphorylation inhibitor decreased spinal p-CaMKII
Evidence Sentence: To investigate the effect of KN-93 on spinal p-CaMKII, the spinal cord was removed from the two groups of rats at day 20 after finishing the behavioral test in KN-93 behavioral experiment.
Evidence Sentence: 6, vehicle of paclitaxel-injected rats showed significantly lower levels of p-CaMKII than paclitaxel-injected rats, which suggests that paclitaxel significantly upregulated the levels of p-CaMKII compared to vehicle control.
Evidence Sentence: KN-93-treated rats showed significantly lower levels of p-CaMKII than KN-92 treated rats, confirming the involvement of CaMKII phosphorylation in CIP.
Evidence Sentence: These results suggest that inhibition of p-CaMKII led to alleviation of paclitaxel-induced mechanical allodynia and hyperalgesia.