Opioidergic effects of transcutaneous electrical nerve stimulation on pain and inflammatory edema in a rat model of ankle sprain
DOI:
https://doi.org/10.1590/1809-2950/16836724032017Keywords:
Transcutaneous Electric Nerve Stimulation, Ankle Injuries, Pain, InflammationAbstract
Although transcutaneous electrical nerve stimulation (TENS) has been proposed to modulate pain and the mechanisms underlying analgesia remain poorly understood, evidence of anti-inflammatory effect is more limited. The purpose of this study was to examine the opioidergic mechanisms of TENS effects in two different frequencies on pain and inflammatory edema in the ankle sprain model in rats. Threshold to mechanical stimulation was utilized to examine the changes produced by intraperitoneal injection of non-selective opioid antagonist naloxone on the antihyperalgesic effect induced by a 20-min period of 2Hz or 100Hz TENS in the ankle sprain model, produced by manually overextending the lateral ligaments. Ankle sprain induced a long-lasting reduction in paw withdrawn latency (PWL) after 30 minutes for up to 24 hours in sham TENS (SH-TENS) treated rats. The reduced PWL after the induction of ankle sprain was restored partially at 0,1,2,3 and 6, but not 24 hours, after the termination of 2 Hz-TENS (LF-TENS). In 100Hz (HF-TENS) the reduction in PWL was shorter than LF-TENS and both LF and HF effects were fully blocked in naloxone-treated rats. LF- and HF-TENS treated rats did not reach the elevation of edema and presented a progressive edema reduction for over 24 hours when compared to SH-TENS group. Both effects were reduced by naloxone. TENS-induced antihyperalgesic and anti-edematous effects observed in ankle sprain model were mediated by the endogenous opioid system.Downloads
References
Chesterton LS, Foster NE, Wright CC, Baxter DG, Barlas
P. Effects of TENS frequency, intensity and stimulation
site parameter manipulation on pressure pain thresholds
in healthy human subjects. Pain. 2003;106(1-2):73-80.
doi: 10.1016/S0304-3959(03)00292-6.
Ellrich J, Lamp S. Peripheral nerve stimulation inhibits
nociceptive processing: an electrophysiological study in
healthy volunteers. Neuromodulation. 2005;8(4):225-32. doi:
1111/j.1525-1403.2005.00029.x.
Krabbenbos IP, Brandsma D, van Swol CF, Boezeman EH,
Tromp SC, Nijhuis HJ, et al. Inhibition of cortical laserevoked potentials by transcutaneous electrical nerve
stimulation. Neuromodulation. 2009;12(2):141-5. doi:
1111/j.1525-1403.2009.00204.x.
Ristić D, Spangenberg P, Ellrich J. Analgesic and
antinociceptive effects of peripheral nerve neurostimulation
in an advanced human experimental model. Eur J Pain.
;12(4):480-90. doi: 10.1016/j.ejpain.2007.07.013.
Vassal F, Créac’h C, Convers P, Laurent B, Garcia-Larrea L,
Peyron R. Modulation of laser-evoked potentials and pain
perception by Transcutaneous Electrical Nerve Stimulation
(TENS): a placebo-controlled study in healthy volunteers.
Clin Neurophysiol. 2013;124(9):1861-7. doi: 10.1016/j.
clinph.2013.04.001.
Garrison DW, Foreman RD. Effects of Transcutaneous
Electrical Nerve Stimulation (TENS) electrode placement
on spontaneous and noxiously evoked dorsal horn cell activity in the cat. Neuromodulation. 2002;5(4):231-7.
doi: 10.1046/j.1525-1403.2002.02036.x.
Melzack R, Wall PD. Pain mechanisms: a new theory. Science.
;150(3699):971-9.
Sluka KA, Bailey K, Bogush J, Olson R, Ricketts A. Treatment
with either high or low frequency TENS reduces the
secondary hyperalgesia observed after injection of kaolin
and carrageenan into the knee joint. Pain. 1998;77(1):97-102.
doi: 10.1016/S0304-3959(98)00090-6.
Radhakrishnan R, King EW, Dickman JK, Herold CA,
Johnston NF, Spurgin ML, et al. Spinal 5-HT2
and 5-HT3
receptors mediate low, but not high, frequency TENSinduced antihyperalgesia in rats. Pain. 2003;105(1-2):205-13.
doi: 10.1016/S0304-3959(03)00207-0.
Zhang RX, Lao L, Wang L, Liu B, Wang X, Ren K, et al.
Involvement of opioid receptors in electroacupunctureproduced anti-hyperalgesia in rats with peripheral
inflammation. Brain Res. 2004;1020(1-2):12-7. doi: 10.1016/j.
brainres.2004.05.067.
Zhang RX, Wang L, Liu B, Qiao JT, Ren K, Berman BM,
et al. Mu opioid receptor-containing neurons mediate
electroacupuncture-produced anti-hyperalgesia in rats with
hind paw inflammation. Brain Res. 2005;1048(1-2):235-40.
doi: 10.1016/j.brainres.2005.05.008.
Taguchi R, Taguchi T, Kitakoji H. Involvement of peripheral
opioid receptors in electroacupuncture analgesia for
carrageenan-induced hyperalgesia. Brain Res. 2010;1355:97-
doi: 10.1016/j.brainres.2010.08.014.
Wang Y, Hackel D, Peng F, Rittner HL. Long-term
antinociception by electroacupuncture is mediated via
peripheral opioid receptors in free-moving rats with
inflammatory hyperalgesia. Eur J Pain. 2013;17(10):1447-57.
doi: 10.1002/j.1532-2149.2013.00325.x.
Woolf CJ, Mitchell D, Barrett GD. Antinociceptive effect of
peripheral segmental electrical stimulation in the rat. Pain.
;8(2):237-52. doi: 10.1016/0304-3959(88)90011-5.
Daher JB, de Melo MD, Tonussi CR. Evidence for a spinal
serotonergic control of the peripheral inflammation in the rat.
Life Sci. 2005;76(20):2349-59. doi: 10.1016/j.lfs.2004.11.012.
Daher JB, Tonussi CR. A spinal mechanism for the peripheral
anti-inflammatory action of indomethacin. Brain Res.
;962(1-2):207-12. doi: 10.1016/S0006-8993(02)04056-8.
Willis WD Jr. Dorsal root potentials and dorsal root reflexes: a
double-edged sword. Exp Brain Res. 1999;124(4):395-421.
Chen YW, Tzeng JI, Lin MF, Hung CH, Wang JJ. Transcutaneous
electrical nerve stimulation attenuates postsurgical allodynia
and suppresses spinal substance P and proinflammatory
cytokine release in rats. Phys Ther. 2015;95(1):76-85.
doi: 10.2522/ptj.20130306.
Kim HY, Koo ST, Kim JH, An K, Chung K, Chung JM.
Electroacupuncture analgesia in rat ankle sprain pain model:
neural mechanisms. Neurol Res. 2010;32(Suppl 1):10-7.
doi: 10.1179/016164109X12537002793689.
Koo ST, Park YI, Lim KS, Chung K, Chung JM. Acupuncture
analgesia in a new rat model of ankle sprain pain. Pain.
;99(3):423-31. doi: 10.1016/S0304-3959(02)00164-1.
Brock SC, Tonussi CR. Intrathecally injected morphine
inhibits inflammatory paw edema: the involvement of nitric
oxide and cyclic-guanosine monophosphate. Anesth Analg.
;106(3):965-71. doi: 10.1213/ane.0b013e318162cebf.
Cunha TM, Verri WA Jr, Valerio DA, Guerrero AT, Nogueira
LG, Vieira SM, et al. Role of cytokines in mediating
mechanical hypernociception in a model of delayed-type
hypersensitivity in mice. Eur J Pain. 2008;12(8):1059-68. doi:
1016/j.ejpain.2008.02.003.
Bennett MI, Hughes N, Johnson MI. Methodological quality in
randomised controlled trials of transcutaneous electric nerve
stimulation for pain: low fidelity may explain negative findings.
Pain. 2011;152(6):1226-32. doi: 10.1016/j.pain.2010.12.009.
Sluka KA, Walsh D. Transcutaneous electrical nerve
stimulation: basic science mechanisms and clinical
effectiveness. J Pain. 2003;4(3):109-21. doi: 10.1054/
jpai.2003.434.
Millan MJ. Descending control of pain. Prog Neurobiol.
;66(6):355-474. doi: 10.1016/S0301-0082(02)00009-6.
Cunha TM, Roman-Campos D, Lotufo CM, Duarte HL,
Souza GR, Verri WA Jr, et al. Morphine peripheral analgesia
depends on activation of the PI3Kgamma/AKT/nNOS/
NO/KATP signaling pathway. Proc Natl Acad Sci U S A.
;107(9):4442-7. doi: 10.1073/pnas.0914733107.
Fields HL, Emson PC, Leigh BK, Gilbert RF, Iversen LL.
Multiple opiate receptor sites on primary afferent fibres.
Nature. 1980;284(5754):351-3. doi: 10.1038/284351a0.
Wybran J. Enkephalins and endorphins as modifiers of the
immune system: present and future. Fed Proc. 1985;44(1 Pt
:92-4.
Carr DJ, DeCosta BR, Kim CH, Jacobson AE, Guarcello V,
Rice KC, et al. Opioid receptors on cells of the immune
system: evidence for delta- and kappa-classes. J Endocrinol.
;122(1):161-8.
Kapitzke D, Vetter I, Cabot PJ. Endogenous opioid analgesia
in peripheral tissues and the clinical implications for pain
control. Ther Clin Risk Manag. 2005;1(4):279-97.
Kulkarni-Narla A, Walcheck B, Brown DR. Opioid receptors on
bone marrow neutrophils modulate chemotaxis and CD11b/
CD18 expression. Eur J Pharmacol. 2001;414(2-3):289-94.
Toda K. Response of raphe magnus neurons after acupuncture
stimulation in rat. Brain Res. 1982;242(2):350-3.
Heinricher MM, Tavares I, Leith JL, Lumb BM. Descending
control of nociception: specificity, recruitment and
plasticity. Brain Res Rev. 2009;60(1):214-25. doi: 10.1016/j.
brainresrev.2008.12.009.
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