The role of Toll-like receptors in pain control
Journal of Cellular & Molecular Anesthesia,
Vol. 2 No. 1 (2017),
1 January 2017
,
Page 24-29
https://doi.org/10.22037/jcma.v2i1.14970
Abstract
The Toll like (family of receptors TLR) are expressed primarily by immune cells and are known to be part of innate immune system. In the past decade involvement of TLRs in several physiologic and pathologic pathways has been proved. Pain transmission via glial activation is one of such interesting fields. Both pathological pain states and treatment have also been shown to be related to TLR-related pathways. Opioid agonists are found to possess TLR4 agonistic effects and glial activity. Targeting TLRs could be a novel method for treatment of neuropathic pain. Moreover attenuation of glial activation by the aim of selective TLR antagonistic drugs, may become a preferred way of separating the beneficial (analgesia) and unwanted effects of opioids, improving their safety and efficacy.
- Toll-like receptors
- pain control
- TLR
How to Cite
References
Anders HJ, Banas B, Schlondorff D. Signaling danger: Toll-like receptors and their potential roles in kidney disease. J Am Soc Nephrol. 2004;15 (4):854-67.
Austin PJ, Moalem-Taylor G. The neuro-immune balance in neuropathic pain: involvement of inflammatory immune cells, immune-like glial cells and cytokines. J Neuroimmunol. 2010;229 (1-2):26-50.
Peirs C, Seal RP. Targeting Toll-like receptors to treat chronic pain. Nat Med. 2015;21 (11):1251-2.
Milligan ED, Watkins LR. Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci. 2009;10 (1):23-36.
Ozinsky A, Smith KD, Hume D, Underhill DM. Co-operative induction of pro-inflammatory signaling by Toll-like receptors. J Endotoxin Res. 2000;6 (5):393-6.
Takeda K, Akira S. Regulation of innate immune responses by Toll-like receptors. Jpn J Infect Dis. 2001;54 (6):209-19.
Jin MS, Lee JO. Structures of the toll-like receptor family and its ligand complexes. Immunity. 2008;29 (2):182-91.
Kang JY, Lee JO. Structural biology of the Toll-like receptor family. Annu Rev Biochem. 2011;80:917-41.
Botos I, Segal DM, Davies DR. The structural biology of Toll-like receptors. Structure. 2011;19 (4):447-59.
Carr DB, Goudas LC. Acute pain. Lancet. 1999;353 (9169):2051-8.
Hunt SP, Mantyh PW. The molecular dynamics of pain control. Nat Rev Neurosci. 2001;2 (2):83-91.
Hucho T, Levine JD. Signaling pathways in sensitization: toward a nociceptor cell biology. Neuron. 2007;55 (3):365-76.
Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000;288 (5472):1765-9.
Petrenko AB, Yamakura T, Baba H, Shimoji K. The role of N-methyl-D-aspartate (NMDA) receptors in pain: a review. Anesth Analg. 2003;97 (4):1108-16.
Ren K, Dubner R. Interactions between the immune and nervous systems in pain. Nat Med. 2010;16 (11):1267-76.
Zimmermann M. Pathobiology of neuropathic pain. Eur J Pharmacol. 2001;429 (1-3):23-37.
Hutchinson MR, Zhang Y, Brown K, Coats BD, Shridhar M, Sholar PW, et al. Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4). Eur J Neurosci. 2008;28 (1):20-9.
Buchanan MM, Hutchinson M, Watkins LR, Yin H. Toll-like receptor 4 in CNS pathologies. J Neurochem. 2010;114 (1):13-27.
Miyake K. Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. Semin Immunol. 2007;19 (1):3-10.
Tanga FY, Raghavendra V, DeLeo JA. Quantitative real-time RT-PCR assessment of spinal microglial and astrocytic activation markers in a rat model of neuropathic pain. Neurochem Int. 2004;45 (2-3):397-407.
Husemann J, Loike JD, Anankov R, Febbraio M, Silverstein SC. Scavenger receptors in neurobiology and neuropathology: their role on microglia and other cells of the nervous system. Glia. 2002;40 (2):195-205.
Ledeboer A, Sloane EM, Milligan ED, Frank MG, Mahony JH, Maier SF, et al. Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain. 2005;115 (1-2):71-83.
Watkins LR, Hutchinson MR, Ledeboer A, Wieseler-Frank J, Milligan ED, Maier SF. Norman Cousins Lecture. Glia as the "bad guys": implications for improving clinical pain control and the clinical utility of opioids. Brain Behav Immun. 2007;21 (2):131-46.
Hutchinson MR, Loram LC, Zhang Y, Shridhar M, Rezvani N, Berkelhammer D, et al. Evidence that tricyclic small molecules may possess toll-like receptor and myeloid differentiation protein 2 activity. Neuroscience. 2010;168 (2):551-63.
Johnston IN, Milligan ED, Wieseler-Frank J, Frank MG, Zapata V, Campisi J, et al. A role for proinflammatory cytokines and fractalkine in analgesia, tolerance, and subsequent pain facilitation induced by chronic intrathecal morphine. J Neurosci. 2004;24 (33):7353-65.
Hutchinson MR, Zhang Y, Shridhar M, Evans JH, Buchanan MM, Zhao TX, et al. Evidence that opioids may have toll-like receptor 4 and MD-2 effects. Brain Behav Immun. 2010;24 (1):83-95.
Nicotra L, Loram LC, Watkins LR, Hutchinson MR. Toll-like receptors in chronic pain. Exp Neurol. 2012;234 (2):316-29.
Thomas J, Hutchinson MR. Exploring neuroinflammation as a potential avenue to improve the clinical efficacy of opioids. Expert Rev Neurother. 2012;12 (11):1311-24.
Hutchinson MR, Bland ST, Johnson KW, Rice KC, Maier SF, Watkins LR. Opioid-induced glial activation: mechanisms of activation and implications for opioid analgesia, dependence, and reward. ScientificWorldJournal. 2007;7:98-111.
Shavit Y, Wolf G, Goshen I, Livshits D, Yirmiya R. Interleukin-1 antagonizes morphine analgesia and underlies morphine tolerance. Pain. 2005;115 (1-2):50-9.
Watkins LR, Hutchinson MR, Rice KC, Maier SF. The "toll" of opioid-induced glial activation: improving the clinical efficacy of opioids by targeting glia. Trends Pharmacol Sci. 2009;30 (11):581-91.
Watkins LR, Hutchinson MR, Milligan ED, Maier SF. "Listening" and "talking" to neurons: implications of immune activation for pain control and increasing the efficacy of opioids. Brain Res Rev. 2007;56 (1):148-69.
Savage SR. Opioid therapy of chronic pain: assessment of consequences. Acta Anaesthesiol Scand. 1999;43 (9):909-17.
Sees KL, Clark HW. Opioid use in the treatment of chronic pain: assessment of addiction. J Pain Symptom Manage. 1993;8 (5):257-64.
- Abstract Viewed: 381 times
- PDF Downloaded: 368 times