Neuropeptide Y tonically inhibits an NMDAR➔AC1➔TRPA1/TRPV1 mechanism of the affective dimension of chronic neuropathic pain

Fu, Weisi; Wessel, Caitlin R.; Taylor, Bradley K.

doi:10.1016/j.npep.2020.102024

Cited by 12 publications

(13 citation statements)

References 41 publications

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“…We found increased mRNA levels of neuropeptide Y and substance P in the spinal cord 7 days after CCI in mice, in contrast to CGRP. Both upregulated neuropeptides are strongly involved in the pathogenesis of neuropathic pain [21,22]. They are released in the spinal dorsal horn by primary sensory afferent neurons, which contributes to their hypersensitivity [21,22].…”

Section: Discussionmentioning

confidence: 99%

Mirogabalin Decreases Pain-like Behaviours and Improves Opioid and Ketamine Antinociception in a Mouse Model of Neuropathic Pain

et al. 2022

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Neuropathic pain remains a difficult clinical challenge due to its diverse aetiology and complex pathomechanisms, which are yet to be fully understood. Despite the variety of available therapies, many patients suffer from ineffective pain relief; hence, the search for more efficacious treatments continues. The new gabapentinoid, mirogabalin has recently been approved for clinical use. Although its main mechanism of action occurs at the α2σ-1 and α2σ-2 subunits of calcium channels and is well documented, how the drug affects the disturbed neuropathic interactions at the spinal cord level has not been clarified, which is crucial information from a clinical perspective. The findings of our study suggest that several indirect mechanisms may be responsible for the beneficial analgesic effect of mirogabalin. This is the first study to report that mirogabalin enhances the mRNA expression of spinal antinociceptive factors, such as IL-10 and IL-18BP, and reduces the concentration of the pronociceptive substance P. Importantly, mirogabalin improves the morphine-, buprenorphine-, oxycodone-, and ketamine-induced antinociceptive effects in a neuropathic pain model. Our findings support the hypothesis that enhancing opioid and ketamine analgesia by combining these drugs with mirogabalin may represent a new strategy for the effective pharmacotherapy of neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

Mirogabalin Decreases Pain-like Behaviours and Improves Opioid and Ketamine Antinociception in a Mouse Model of Neuropathic Pain

et al. 2022

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“…The effect of mirogabalin was likely due to its effect specifically on pain perception rather than potential reinforcing properties it may have as observed with opioids. Actually, gabapentinoids do not appear to induce preference in sham-operated mice [ 24 ]. In other rodent models of neuropathic pain, antinociceptive treatment induces CPP as well as reductions in nerve injury-induced pain-related behavior [ 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

Pretreatment with High Mobility Group Box-1 Monoclonal Antibody Prevents the Onset of Trigeminal Neuropathy in Mice with a Distal Infraorbital Nerve Chronic Constriction Injury

Kochi

Nakamura

et al. 2021

Molecules

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Persistent pain following orofacial surgery is not uncommon. High mobility group box 1 (HMGB1), an alarmin, is released by peripheral immune cells following nerve injury and could be related to pain associated with trigeminal nerve injury. Distal infraorbital nerve chronic constriction injury (dIoN-CCI) evokes pain-related behaviors including increased facial grooming and hyper-responsiveness to acetone (cutaneous cooling) after dIoN-CCI surgery in mice. In addition, dIoN-CCI mice developed conditioned place preference to mirogabalin, suggesting increased neuropathic pain-related aversion. Treatment of the infraorbital nerve with neutralizing antibody HMGB1 (anti-HMGB1 nAb) before dIoN-CCI prevented both facial grooming and hyper-responsiveness to cooling. Pretreatment with anti-HMGB1 nAb also blocked immune cell activation associated with trigeminal nerve injury including the accumulation of macrophage around the injured IoN and increased microglia activation in the ipsilateral spinal trigeminal nucleus caudalis. The current findings demonstrated that blocking of HMGB1 prior to nerve injury prevents the onset of pain-related behaviors, possibly through blocking the activation of immune cells associated with the nerve injury, both within the CNS and on peripheral nerves. The current findings further suggest that blocking HMGB1 before tissue injury could be a novel strategy to prevent the induction of chronic pain following orofacial surgeries.

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“…Recently, latent pain sensitization was identified in other well-established models of persistent pain, as paw plantar incision (Campillo et al, 2011;Romero-Alejo et al, 2016b), nerve injury (Chen & Marvizón, 2020a, 2020bFu et al, 2020;Solway et al, 2011), carrageenan-(Le Roy et al, 2011 or Complete Freund's Adjuvant (CFA)-induced inflammatory pain (Araldi et al, 2017;Chen et al, 2018b;Chen & Marvizón, 2020a, 2020bCorder et al, 2013;Feehan & Zadina, 2019;Marvizón et al, 2015;Severino et al, 2018;Solway et al, 2011;Taylor et al, 2019;Walwyn et al, 2016) and Nerve Growth Factor (NGF) induced non-specific low back pain (Zhang et al, 2017). Thus, nociceptive inputs can also indirectly stimulate endogenous opioid system to initiate sustained latent sensitization to pain.…”

Section: Animal Models Of Latent Pain Sensitizationmentioning

confidence: 99%

“…Y2 (but not Y1) antagonist induces pERK and c-fos upregulation in LI-LII spinal laminae following CFAinduced hyperalgesia resolution (Solway et al, 2011), confirming its role as an anti-nociceptive system. Finally, NPY involvement in latent pain sensitization is not restricted to nociception and extends to the unpleasant and uncomfortable component of pain, as assessed by the conditioned place aversion produced by an intrathecal administration of Y1 antagonist and in NPY conditional knock-down (Fu et al, 2020).…”

Section: Neuropeptide Y (Npy) and Its Y1 -Y2 Receptorsmentioning

confidence: 99%

“…This NMDA-R -TRPA1 / TRPV1 signaling pathway is also involved in affective pain dimension reinstatement. Indeed, conditioned place aversion induced by Y1 antagonist or in NPY conditional knock-down mice is blocked by MK-801, AC1 inhibitor, TRPA1, and TRPV1 channel blocker and is absent in AC1 -/-mice in a model of nerve injury (Fu et al, 2020).…”

Section: N-methyl-d-aspartate (Nmda) Receptormentioning

confidence: 99%

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Behavioral characterization, potential clinical relevance and mechanisms of latent pain sensitization

Gerum¹,

Simonin²

2022

Pharmacology & Therapeutics

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Chronic pain is a debilitating disorder that can occur as painful episodes that alternates with bouts of remission and occurs despite healing of the primary insult. Those episodes are often triggered by stressful events. In the last decades, a similar situation has been evidenced in a wide variety of rodent models (including inflammatory pain, neuropathy and opioid-induced hyperalgesia) where animals develop a chronic latent hyperalgesia that silently persists after behavioral signs of pain resolution. This state, referred as latent pain sensitization, is due to the compensatory activation of antinociceptive systems, such as the opioid system or NPY and its receptors. A transitory phase of hyperalgesia can then be reinstated by pharmacological or genetic blockade of these antinociceptive systems or by submitting animals to acute stress. Those observations reveal that there is a constant endogenous analgesia responsible for chronic pain inhibition that might paradoxically contribute to maintain this maladaptive state and could then participate to the transition from acute to chronic pain. Thus, demonstration of the existence of this phenomenon in humans and a better understanding of the mechanisms by which latent pain sensitization develops and maintains over long periods of time will be of particular interest to help identifying new therapeutic strategies and targets for chronic pain treatment. The present review aims to recapitulate behavioral expression, potential clinical relevance, cellular mechanisms and intracellular signaling pathways involved so far in latent pain sensitization.

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Neuropeptide Y tonically inhibits an NMDAR➔AC1➔TRPA1/TRPV1 mechanism of the affective dimension of chronic neuropathic pain

Cited by 12 publications

References 41 publications

Mirogabalin Decreases Pain-like Behaviours and Improves Opioid and Ketamine Antinociception in a Mouse Model of Neuropathic Pain

Mirogabalin Decreases Pain-like Behaviours and Improves Opioid and Ketamine Antinociception in a Mouse Model of Neuropathic Pain

Pretreatment with High Mobility Group Box-1 Monoclonal Antibody Prevents the Onset of Trigeminal Neuropathy in Mice with a Distal Infraorbital Nerve Chronic Constriction Injury

Behavioral characterization, potential clinical relevance and mechanisms of latent pain sensitization

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