Therapeutic potential of combining mirogabalin with antidepressants in relieving hypersensitivity: evidence from a mouse model of neuropathic pain.

Stroke is the leading cause of long-term disability among adults worldwide, with millions of survivors experiencing lasting motor dysfunction that significantly impacts independence, living standards, and community involvement [–]. Deficits in balance and gait are two of the most common and debilitating sequelae, affecting more than 80% of survivors even years after the event. These impairments not only reduce functional mobility but also significantly increase the risk of falls, a serious complication in stroke recovery, with up to 73% of community-dwelling survivors experiencing at least one fall each year [, ]. Falls can lead to secondary injuries, fear of falling, social isolation, institutionalization, and substantial healthcare costs [, ]. Although motor weakness, spasticity, and coordination impairments have continued to take center stage in stroke rehabilitation paradigms, emerging evidence from the last 10 years has highlighted the critical and often under-reported role of somatosensory impairments specifically proprioceptive acuity in the ankle, amid ongoing balance and gait issues [, ]. Proprioception, which involves joint position and movement sense, is essential for controlling posture, weight distribution, and accurate foot placement during walking. In stroke survivors, ankle proprioceptive deficits are widespread and bilateral, and inversion/eversion movements are frequently affected due to biomechanical loading during dynamic stance stability and swing-phase clearance [, ]. Balanced ankle inversion proprioception, assessed with validated tools such as the Active Movement Extent Discrimination Apparatus (AMEDA) [], has consistently been shown to be the strongest independent predictor of balance dysfunction (measured by the Berg Balance Scale) and slower gait speed in individuals that experienced a stroke. It also surpasses traditional predictors such as ankle strength or spasticity [–]. These correlations persist even when accounting for confounding factors, indicating a direct mechanistic connection. Bilateral deficits, often noticeable even on the so-called unaffected side, suggest central rather than peripheral sensorimotor impairments, potentially due to altered cortical somatosensory representation, interhemispheric inhibition, or increased reliance on compensatory visual and vestibular responses. Robotic-assisted ankle positioning, textured surfaces, whole-body vibration, and proprioceptive neuromuscular facilitation are among the approaches reported to improve both proprioceptive acuity and downstream motor outcomes [, –]. Although these cross-sectional results are strong and consistent, several critical gaps hinder their translation into clinical practice. First, causality is not established: it remains unclear whether functional limitations are directly caused by impaired ankle proprioception or if they are simply indicators of extensive neurological injury and spontaneous recovery. Second, the progression of proprioceptive impairment throughout the stroke recovery process including acute, subacute, and chronic stages, has not been well characterized, and it is uncertain whether deficits can stabilize, improve spontaneously, or deteriorate gradually. Third, the generalizability of the observed associations and potential treatment effects among individuals with moderate-to-severe stroke or non-ambulatory status is uncertain because most previous studies do not systematically examine these groups [–].