Chemotherapy-induced pain (CIP) is common in patients who receive anti-neoplastic agents. CIP is not yet adequately controlled, and it results in patient suffering, limits treatment with potentially useful anti-cancer drugs, and significantly affects the quality of life of cancer patients. Acupuncture, which has been used for millennia to treat pain, may alleviate CIP, but its effectiveness against this condition has not been studied and warrants investigation. Paclitaxel, an anti-neoplastic agent widely used to treat cancerous ovarian, breast and non-small cell lung tumors, produces neuropathic pain in humans and in rats. The objective of this study is to evaluate the effects and mechanisms of electroacupuncture (EA) on a paclitaxel-induced CIP rat model with persistent pain for 5 months. The hypothesis is that EA will alleviate the CIP at least in part by enhancing the activity of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter, and consequently blocking pronociceptive cytokine expression in the spinal cord.
The specific aims are:
Aim 1 : Evaluate EA's ability to inhibit CIP. After onset of allodynia on days 14-28 or before the paclitaxel injections and before onset of allodynia on days -2-12, EA treatment will be given at acupoint GB30 or ST30 every other day for two weeks to determine whether it alleviates and/or prevents CIP. We hypothesize that EA will relieve and prevent the CIP.
Aim 2 : Determine whether GABA affects EA alleviation of hyperalgesia/allodynia. The GABA receptor (A &B) antagonists bicuculline and phaclofen will be administered prior to EA treatment. We hypothesize that these antagonists will prevent EA-produced alleviation of CIP.
Aim 3 : Determine whether GABA affects EA inhibition of interleukin-12 (IL-12), tumor necrosis factor-alpha (TNF-1) and IL-6 in spinal cord. EA modulation of these cytokines, which are prototypical pro-inflammatory cytokines involved in pain maintenance, will be investigated in rats with and without GABA receptor antagonist pretreatment. Using western blot and immunostaining, we will examine IL-12, TNF-1 and IL-6 levels, the cell type that produces these cytokines, and the location of cytokine-immunoreactive cells in the spinal cord. We hypothesize that EA will significantly inhibit expression of these cytokines and that pretreatment with GABA receptor antagonists will block the EA effect. These studies will advance our knowledge of, and form the basis of a clinical trial of, the efficacy of EA in treating CIP. The success of the proposed study will greatly advance CIP management. Project Narrative: Chemotherapy-induced pain (CIP) occurs frequently in cancer patients who receive antineoplastic agents and, and has not been controlled adequately. Acupuncture has been used for millennia to treat pain. This study will evaluate the effects and mechanisms of electroacupuncture (EA) on such pain in a rat model. The success of the proposed study will greatly advance the management of CIP.
