Acute morphine blocks spinal respiratory motor plasticity via long‐latency mechanisms that require toll‐like receptor 4 signalling

Abstract

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Opioids, plasticity and phrenic motor performance: investigating the off‐target effects of acute morphine administration

“…Opioids are known to have off‐target effects via their action on TLR4, where they bind to the TLR4‐myeloid differentiation protein‐2 complex, promoting the production of inflammatory cytokines (Tadjalli et al . 2021 a ). The effects of therapeutic opioid use on cervical spinal inflammatory signalling and the implications this may have for phrenic motor plasticity is unclear.…”

“…Indeed, (+)‐naloxone attenuated morphine‐induced blockade of pLTF, revealing a long‐latent off‐target effect of morphine, which blocks this form of respiratory neuroplasticity (Tadjalli et al . 2021 a ).…”

“…p38 MAPK is a regulator of inflammatory signalling, and its activation in spinal phrenic motor neurons and adjacent microglia has previously been shown to undermine pLTF (Huxtable et al 2015). Opioids are known to have off-target effects via their action on TLR4, where they bind to the TLR4-myeloid differentiation protein-2 complex, promoting the production of inflammatory cytokines (Tadjalli et al 2021a). The effects of therapeutic opioid use on cervical spinal inflammatory signalling and the implications this may have for phrenic motor plasticity is unclear.…”

“…In their recent publication in The Journal of Physiology , Tadjalli and colleagues (2021 a ) sought to address three distinct experimental questions: (i) Does acute systemic morphine administration block pLTF? (ii) Does systemic (+)‐naloxone pre‐treatment preserve pLTF following morphine delivery?…”

“…Opioids are known to induce inflammation (Tadjalli et al . 2021 a ), which can compromise respiratory neuroplasticity, namely pLTF (Huxtable et al . 2015).…”