矢島さんfirst authorの「痛覚変調性疼痛」モデルでのアセトアミノフェンとプレガバリンの感作抑制作用を報告した論文が出ました
杉本さんが2021年にPain誌にfirst authorで報告した，口唇部へのホルマリン投与，もしくは，右扁桃体のDREADD活性化が両側の下肢痛覚過敏を生じるという現象を，その部位や支配神経に傷害・障害がないにもかかわらず痛覚過敏が生じる「痛覚変調性疼痛」のモデルととらえ，広く使われ，しかしその作用機序が十分に（あるいはほとんど）わかっていない鎮痛薬の作用を評価した論文がNeuropharmacologyに掲載されました．今後，痛みのメカニズムを理解し，その治療薬を評価・開発していく上でとても重要になるモデルであると考えています．
Manami Yajima, Mariko Sugimoto, Yae K. Sugimura, Yukari Takahashi, Fusao Kato,
Acetaminophen and pregabalin attenuate central sensitization in rodent models of nociplastic widespread pain,
Neuropharmacology, 2022, 109029, ISSN 0028-3908,
https://doi.org/10.1016/j.neuropharm.2022.109029.
(https://www.sciencedirect.com/science/article/pii/S0028390822000880)
Abstract: The “nociplastic pain,” a recently proposed novel mechanistic pain descriptor, is defined as pain occurring through altered nociception without nociceptor activation and nerve injury. Nociplastic pain is often characterized by widespread pain sensitization (WSP) in multiple body regions (Fitzcharles et al., 2021). As many patients with primary chronic pain would have nociplastic backgrounds, developing appropriate methods to evaluate drug effects against nociplastic pain in animal model is in great demand. Using two rat models with the WSP involving central amygdala (CeA) activation by orofacial inflammation or direct chemogenetic activation (Sugimoto et al., 2021), we examined whether widely used analgesics, acetaminophen (AcAph), pregabalin (PGB), and duloxetine (DLX) could attenuate the WSP. AcAph (100 or 200 mg/kg, i.p.) significantly elevated 50%-paw withdrawal threshold (PWT50), which had been lowered significantly by upper lip injection of formalin, or systemic injection of clozapine-N-oxide in the rats with excitatory designer receptors (hM3Dq) expressed in the right CeA. This effect lasted for > ∼4 h. PGB (30 mg/kg, i.p.) also significantly counteracted the lowered PWT50 in rats with orofacial formalin injection for >∼6 h. DLX was ineffective on the WSP. Based on these results, we propose that these preclinical models could be used to evaluate drug effects for primary chronic pain. We conclude that the widely used pain killers, AcAph and PGB, also relieve nociplastic widespread sensitization in the absence of ongoing nociceptor activation and nerve injury.
Keywords: Chemogenetics; von Frey filament test; Central amygdala; Endocannabinoids; TRPV1; Gabapentinoids