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.
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