Electroacupuncture Attenuates Bone Cancer Pain and Inhibits Spinal Interleukin-1β Expression in a Rat Model

Center for Integrative Medicine, School of Medicine, University of Maryland, Baltimore, Maryland 21201, USA.
Anesthesia and analgesia (Impact Factor: 3.47). 11/2007; 105(5):1482-8, table of contents. DOI: 10.1213/01.ane.0000284705.34629.c5
Source: PubMed

ABSTRACT Although pain affects the quality of life of cancer patients, current medical treatments are either ineffective or have side effects. In the present study we investigated the effect of electroacupuncture (EA) on cancer-induced hyperalgesia and expression of interleukin-1beta (IL-1beta), upregulation of which is related to the maintenance of persistent pain, in a rat model of bone cancer pain.
Cancer was induced by injecting AT-3.1 prostate cancer cells into the tibia of male Copenhagen rats. The resulting pain was treated with 10 Hz/2 mA/0.4 ms pulse EA for 30 min daily at the equivalent of the human acupoint GB30 (Huantiao) between Days 14 and 18 after cancer cell inoculation. For sham control, EA needles were inserted into GB30 without stimulation. Thermal hyperalgesia, a decrease in paw withdrawal latency to a noxious thermal stimulus, was measured at baseline and 20 min after EA treatment. IL-1beta and its mRNA were respectively determined by immunohistochemistry and reverse transcription-polymerase chain reaction analysis.
Thermal hyperalgesia developed between Days 12 and 18 after cancer cell inoculation. EA significantly (P < 0.05) attenuated this hyperalgesia, increasing paw withdrawal latency from 7.0 +/- 0.3 s to 9.2 +/- 0.4 s, and inhibited the upregulation of IL-1beta and its mRNA compared to the sham control. Intrathecal injection of IL-1 receptor antagonist (IL-1ra, 0.1 mg/rat) also significantly inhibited cancer-induced thermal hyperalgesia.
The data suggest that EA alleviates bone cancer pain, at least in part by suppressing IL-1beta expression. The results support the clinical use of EA in the treatment of cancer pain.

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    • "In the present study, we demonstrated that the expression levels of proinflammatory cytokines were dramatically decreased after EA stimulation in both the injured peripheral nerves and DRG of neuropathic rats. There were some studies which showed the effect of EA on pain attenuation and inhibition of cytokines expression in the central nervous system using an animal model of cancer pain [27] and on reduction of inflammation-induced cytokine expression by acupuncture using an animal model of carrageenan-induced inflammatory pain [28]. Similar to cancer pain and inflammatory pain, we demonstrated that EA inhibits the expressions of proinflammatory cytokines. "
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    ABSTRACT: The production of proinflammatory cytokines including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor- α (TNF- α ) plays a key role in chronic pain such as neuropathic pain. We investigated changes in cytokine expression in injured peripheral nerves and dorsal root ganglia (DRG) following electroacupuncture (EA) treatment. Neuropathic pain was induced by peripheral nerve injury to the left hind limb of Sprague-Dawley rats under pentobarbital anesthesia. Two weeks later, the nerve-injured rats were treated by EA for 10 minutes. The expression levels of IL-1 β , IL-6, and TNF- α in peripheral nerves and DRG of neuropathic rats were significantly increased in nerve-injured rats. However, after EA, the cytokine expression levels were noticeably decreased in peripheral nerves and DRG. These results suggest that EA stimulation can reduce the levels of proinflamtory cytokines elevated after nerve injury.
    Evidence-based Complementary and Alternative Medicine 02/2012; 2012(8):792765. DOI:10.1155/2012/792765 · 1.88 Impact Factor
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    • "Using rat models of cancer-induced bone pain in the laboratory, it has been shown that daily treatment of electroacupuncture for 30 minutes at 10 Hz/2 mA/0.4 ms pulse for 5 days suppresses both dynorphin and interleukin-1␤ expression in the dorsal horn. As both dynorphin [59] and interleukin-1␤ [60,61] are known to facilitate hyperalgesia, these studies indicate that cancer-induced bone pain may be inhibited by electroacupuncture [62] [63] and the resulting dorsal horn depression can last for days or weeks [54]. Recently, manual acupuncture has also been shown to stimulate connective tissue in rat models, generating a strong afferent input to the dorsal horn which produces the same effect [64] [65]. "
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    ABSTRACT: Patients suffering from pain due to bony metastases in cancer represent a challenge to the physiotherapist as part of the multidisciplinary team. Adequate pain relief improves quality of life and functional status, yet conventional analgesia often has undesirable side-effects and non-pharmacological treatments (e.g. some electrotherapies) may be contraindicated in cancer. Acupuncture is a potential treatment for cancer-induced bone pain (CIBP) as it has few side effects and is relatively easy to administer. There is a dearth of research on the use of acupuncture in treating CIBP and some practitioners express fears about treating cancer patients with acupuncture. To discuss the use of acupuncture for CIBP by reviewing the physiological rationale for using acupuncture to treat CIBP and the risks and benefits of using acupuncture in clinical practice. Evidence was identified by searching seven major databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, AMED and SPORTDiscus. Evidence was synthesised by the authors to raise issues and discussion points within a narrative review framework. Available physiological evidence supports potentially efficacious effects of acupuncture for reduction of CIBP. Clinical literature suggests that acupuncture may be effective as an adjunctive treatment for CIBP and that risks are manageable. However, there is a need for well-designed randomised controlled trials to investigate efficacy and effectiveness in patients. Acupuncture has the potential to provide sustained background analgesia and/or rapid onset analgesia for breakthrough pain if the appropriate points and techniques are used.
    Physiotherapy 09/2011; 97(3):256-63. DOI:10.1016/ · 1.91 Impact Factor
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    • "It should also be noted that our research shows that functional knockdown of TLR4 also reduced spinal microglial activation, and reduced the expression of mRNA for spinal proinflammatory cytokines. A previous study demonstrated that IL-1β was upregulated in a bone cancer pain rat model and that intrathecal IL-1ra produced an anti-pain effect in such a model [13,25]. The CNS innate immune response includes rapid activation of immune effectors cells and the release of proinflammatory cytokines, such as TNF-α, IL-1 β, IL-6, and IFN-β, through the activation of TLR4-MyD88-dependent or -independent pathways [26]. "
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    ABSTRACT: This study demonstrates a critical role in CNS innate immunity of the microglial Toll-like receptor 4 (TLR4) in the induction and maintenance of behavioral hypersensitivity in a rat model of bone cancer pain with the technique of RNA interference (RNAi). We hypothesized that after intramedullary injection of Walker 256 cells (a breast cancer cell line) into the tibia, CNS neuroimmune activation and subsequent cytokine expression are triggered by the stimulation of microglial membrane-bound TLR4. We assessed tactile allodynia and spontaneous pain in female Sprague-Dawley (SD) rats after intramedullary injection of Walker 256 cells into the tibia. In a complementary study, TLR4 small interfering RNA(siRNA) was administered intrathecally to bone cancer pain rats to reduce the expression of spinal TLR4. The bone cancer pain rats treated with TLR4 siRNA displayed significantly attenuated behavioral hypersensitivity and decreased expression of spinal microglial markers and proinflammatory cytokines compared with controls. Only intrathecal injection of TRL4 siRNA at post-inoculation day 4 could prevent initial development of bone cancer pain; intrathecal injection of TRL4 siRNA at post-inoculation day 9 could attenuate, but not completely block, well-established bone cancer pain. TLR4 might be the main mediator in the induction of bone cancer pain. Further study of this early, specific, and innate CNS/microglial response, and how it leads to sustained glial/neuronal hypersensitivity, might lead to new therapies for the prevention and treatment of bone cancer pain syndromes.
    Molecular Pain 01/2010; 6(1):2. DOI:10.1186/1744-8069-6-2 · 3.65 Impact Factor
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