Transforming preservice teachers' emotions and appraisals on outdoor learning in early childhood education.

Neuropathic pain remains a very serious clinical problem, affecting up to 7–10% of the population, impacting not only the physical but also the mental health of patients [–]. This type of pain results from both damage to and diseases of the sensory–somatic nervous system [, ]. First-line therapies include gabapentinoids (e.g., gabapentin, pregabalin), which target voltage-gated calcium channels (VGCCs), tricyclic antidepressants (TCAs; e.g., amitriptyline), and serotonin-norepinephrine reuptake inhibitors (SNRIs; e.g., duloxetine) [, , ]. Notably, clinical data indicate that neuropathic pain treatment is effective in only 30–50% of patients []. Therefore, experimental research is being conducted to identify innovative drugs and effective combinations of new and old drugs that could be used clinically to improve this unfavorable situation. One such new drug recently introduced in some Asian countries into clinical practice is mirogabalin [–], a gabapentinoid that, compared with clinically used drugs (gabapentin/pregabalin), binds with greater strength and selectivity to the α2δ-1/α2δ-2 subunits of VGCCs []. Data from the literature indicate that mirogabalin has better anti-nociceptive properties and reduces the incidence of adverse effects compared with gabapentin and pregabalin []. In 2019, mirogabalin was approved in Japan for the treatment of postherpetic neuralgia and diabetic neuropathy []. The prospective, multi-center study conducted in Japan in 2021 demonstrated that switching from pregabalin to mirogabalin is well tolerated and effective for the treatment of neuropathic pain []. The second key group of drugs used as first-line treatments are TCAs and SNRIs, which diminish nociceptive transmission by inhibiting serotonin and norepinephrine reuptake [, ]. Amitriptyline, a medication from the TCA group, is frequently used to treat neuropathic pain []. For patients who may be intolerant to TCAs, SNRIs such as duloxetine are alternatives that are typically chosen because of their favorable side effect profile compared with those of other drugs []. The choice among gabapentinoids, TCAs, and SNRIs requires an individualized approach, considering patient-specific factors such as comorbidities, age, pain characteristics, and failures or successes of the prior treatment [, , ]. Importantly, when monotherapy does not provide sufficient pain relief, combinations of gabapentinoids with TCAs or SNRIs are often used [, , , –]. To date, experimental data on the effects of combining mirogabalin with other medications are very sparse. Our previous study conducted in rodents demonstrated for the first time that mirogabalin relieves hypersensitivity when administered alone, but its anti-nociceptive effect is enhanced when it is coadministered with opioid drugs (morphine, buprenorphine, oxycodone) in a mouse model of neuropathic pain []. In 2025, clinical trials confirmed the efficacy of mirogabalin in cancer patients and its beneficial effects when combined with different opioid drugs. Furthermore, compared with pregabalin, mirogabalin with opioids contributes less to drowsiness and dizziness in patients [].