Peripheral inflammation affects modulation of nociceptive synaptic transmission in the spinal cord induced by N‐arachidonoylphosphatidylethanolamine

Abstract

This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc.

CB1 receptor‐dependent desensitisation of TRPV1 channels contributes to the analgesic effect of dipyrone in sensitised primary sensory neurons

“…Importantly, inflammation‐associated “switching” from an exclusively CB 1 receptor‐mediated, to a mixed CB 1 receptor‐ and TRPV1‐mediated, inhibitory effect, as we found in the present study, has been reported at the central terminals of nociceptive primary sensory neurons (Nerandzic et al, 2018). This effect could be due to inflammation‐induced change in the CB 1 receptor–TRPV1 channel protein–protein interaction in a major sub‐population of primary sensory neurons (Chen et al, 2016).…”

Recent advances in targeting ion channels to treat chronic pain

“…The spinal cord dorsal horn slice preparation represents a useful ex vivo preparation to investigate pain pathways. Electrophysiology is again the primary technique, largely focussing on recordings of excitatory (glutamatergic) or inhibitory (GABAergic and/or glycinergic) postsynaptic currents from lamina I and/or II neurons in the superficial dorsal horn (Nerandzic et al ., ; Winters et al ., ). It is also possible to co‐culture DRG and spinal cord neurons to investigate nociceptive function (Yu et al ., ).…”

“…Of relevance here is that a range of animal models of pain are used to determine the effects of potential analgesics on parameters such as hypersensitivity and allodynia and on parameters related to central sensitization such as wind‐up (an activity‐dependent persistent increase in neuronal firing). These models of chronic pain include not only the widely used spinal nerve ligation, partial sciatic nerve ligation and chronic constriction injury models but also more specific models such as Freund's complete adjuvant‐induced inflammatory pain (Lee et al ., ), the carrageenan model of peripheral inflammation (Nerandzic et al ., ), post‐surgical pain and HIV‐induced sensory neuropathy models (Moutal et al ., ) and the chronic visceral hypersensitivity model (Castro et al ., ).…”

“…Initial studies on TRPV1 antagonists were hampered by thermoregulatory side effects; however, capsaicin, delivered via patches, has shown therapeutic value via agonist (and subsequent local sensory nerve terminal retraction) actions. Modulation of TRPV1 channels by endogenous agents such as the lipid precursor N‐arachidonoyl phosphatidylethanolamine (Nerandzic et al ., ) may open further avenues for drug development. Small molecule development has led to trials of antagonists of TRPA1 and TRPM8 channels, while preclinical promise has also been shown for agents targeting TRPV3, TRPV4, TRPM2 and TRPM3 (Moran and Szallasi, ).…”

Hypersensitivity Induced by Intrathecal Bradykinin Administration Is Enhanced by N-oleoyldopamine (OLDA) and Prevented by TRPV1 Antagonist

“…Activation of the TRPV1 receptors localized in periphery is beneficial, following application of high-concentration capsaicin (TRPV1 agonist) patches that are widely used, especially in the treatment of postherpetic neuralgia, HIV-associated neuropathic pain, or musculoskeletal pain [ 7 , 8 ]. In comparison, spinal TRPV1 represent a possible therapeutic target [ 9 ], as they are involved in the development of several pathological pain states [ 5 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ].…”