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ABSTRACT
Introduction. Using a persistent inflammatory pain rat model, we investigated
and separately assessed the mechanisms of electroacupuncture (EA) anti-hyperalgesia
and anti-inflammation. Behavioral studies showed that the effects of EA are
parameter-dependant and distinct in hyperalgesia and inflammation. We hypothesize
that these effects are mediated, respectively, by the hormonal (HPA) and neural
pathways.
Materials and Methods. Male Sprague–Dawley rats were divided into EA and
sham EA groups (n=8-10/group). Complete Freund’s adjuvant (CFA) was injected
into the hind paw of the rat to induce hyperalgesia and edema. EA was performed at
acupoint GB30 in unrestrained, unsedated, conscious animals. Hyperalgesia was
assessed by paw withdrawal latency to a noxious thermal stimulus, and paw edema
was measured with a caliper. Blood samples were collected for ELISA essay, and
spinal and supraspinal tissues were harvested for immunohistochemistry study.
Results. The HPA Pathway. 1) At the adrenal level, EA significantly elevated plasma
corticosterone and decreased paw edema compared to sham EA. The anti-edema
effect was eradicated by adrenalectomy or pretreatment with the corticosterone
antagonist RU486, but neither treatment blocked the anti-hyperalgesic effect of EA. 2)
At the pituitary level, EA significantly increased the plasma adrenocorticotropic
hormone (ACTH), while the ACTH receptor antagonist ACTH(11-24) blocked EA
anti-edema but not EA anti-hyperalgesia. 3) At the hypothalamic level, a CRF
(corticotropin-releasing factor) receptor antagonist, astressin, blocked EA anti-edema
but only partially blocked EA anti-hyperalgesia.
The Neural Pathway. 1) At the spinal level, EA significantly inhibited
CFA-induced Fos expression in the spinal dorsal horn. Pharmacological studies show
that EA anti-hyperalgesia was mediated by mu and delta but not kappa opioid
receptors. Lesioning the G-protein-coupled receptor with pertussis toxin blocked EA
anti-hyperalgesia. Specifically, mu receptor-containing spinal neurons lesioned with dermorphin-saporin showed this effect. Furthermore, a dorsolateral funiculus lesion in
the lower thoracic spinal cord diminished the effect of EA anti-hyperalgesia. 2) At the
supraspinal level, EA activated serotonin- or tyrosine hydroxylase-containing neurons
in the nucleus raphe magnus and locus coeruleus, which project to the spinal cord.
Conclusion. EA-produced anti-hyperalgesia is mainly mediated by sensory
nerve pathways involving spinal and supraspinal mechanisms, while EA-produced
anti-inflammation is mainly mediated by HPA axis activation. These data demonstrate
that acupuncture treats inflammatory pain by restoring homeostasis in the body.
Keywords: electroacupuncture, inflammation, hyperalgesia, animal model
Introduction. Using a persistent inflammatory pain rat model, we investigated
and separately assessed the mechanisms of electroacupuncture (EA) anti-hyperalgesia
and anti-inflammation. Behavioral studies showed that the effects of EA are
parameter-dependant and distinct in hyperalgesia and inflammation. We hypothesize
that these effects are mediated, respectively, by the hormonal (HPA) and neural
pathways.
Materials and Methods. Male Sprague–Dawley rats were divided into EA and
sham EA groups (n=8-10/group). Complete Freund’s adjuvant (CFA) was injected
into the hind paw of the rat to induce hyperalgesia and edema. EA was performed at
acupoint GB30 in unrestrained, unsedated, conscious animals. Hyperalgesia was
assessed by paw withdrawal latency to a noxious thermal stimulus, and paw edema
was measured with a caliper. Blood samples were collected for ELISA essay, and
spinal and supraspinal tissues were harvested for immunohistochemistry study.
Results. The HPA Pathway. 1) At the adrenal level, EA significantly elevated plasma
corticosterone and decreased paw edema compared to sham EA. The anti-edema
effect was eradicated by adrenalectomy or pretreatment with the corticosterone
antagonist RU486, but neither treatment blocked the anti-hyperalgesic effect of EA. 2)
At the pituitary level, EA significantly increased the plasma adrenocorticotropic
hormone (ACTH), while the ACTH receptor antagonist ACTH(11-24) blocked EA
anti-edema but not EA anti-hyperalgesia. 3) At the hypothalamic level, a CRF
(corticotropin-releasing factor) receptor antagonist, astressin, blocked EA anti-edema
but only partially blocked EA anti-hyperalgesia.
The Neural Pathway. 1) At the spinal level, EA significantly inhibited
CFA-induced Fos expression in the spinal dorsal horn. Pharmacological studies show
that EA anti-hyperalgesia was mediated by mu and delta but not kappa opioid
receptors. Lesioning the G-protein-coupled receptor with pertussis toxin blocked EA
anti-hyperalgesia. Specifically, mu receptor-containing spinal neurons lesioned with dermorphin-saporin showed this effect. Furthermore, a dorsolateral funiculus lesion in
the lower thoracic spinal cord diminished the effect of EA anti-hyperalgesia. 2) At the
supraspinal level, EA activated serotonin- or tyrosine hydroxylase-containing neurons
in the nucleus raphe magnus and locus coeruleus, which project to the spinal cord.
Conclusion. EA-produced anti-hyperalgesia is mainly mediated by sensory
nerve pathways involving spinal and supraspinal mechanisms, while EA-produced
anti-inflammation is mainly mediated by HPA axis activation. These data demonstrate
that acupuncture treats inflammatory pain by restoring homeostasis in the body.
Keywords: electroacupuncture, inflammation, hyperalgesia, animal model
