The Expression of α-SMA in the Painful Traumatic Neuroma: Potential Role in the Pathobiology of Neuropathic Pain

The exact mechanism of neuroma-associated pain is not yet fully understood, thus contributing to the substantial challenge faced in managing patients with painful neuromas. We aimed to observe the expression of alpha smooth muscle actin (alpha-SMA) in the painful traumatic neuroma and to investigate its possible roles in the cause of neuroma-associated pain. Its expression is considered to be a useful phenotypic marker for myofibroblast, and may contribute to its increased contractile activity. We collected peripheral neuroma specimens prospectively and subsequently divided them into two groups: painful (n = 21) and non-painful (n = 27) based on blinded preoperative visual analogue scale (VAS) pain scores. We also harvested normal nerve specimens from the discarded limbs as a control group (n = 8). We performed immunohistological studies to observe the expression of alpha-SMA in each group, and calculated the expression level by a high-resolution pathological image analysis system. There was no positive staining of alpha-SMA observed in the control group, slight positive staining in the non-painful group, and obviously positive staining in the painful group. Pearson correlation analysis demonstrated that VAS scores were significantly associated with the expression intensity of alpha-SMA (R = 0.831; p < 0.001). Linear regression analysis indicated that the expression intensity of alpha-SMA was positively related to the scale of VAS (R-2 = 0.691, p < 0.001). These findings suggest that: 1) expression of alpha-SMA may play certain roles in painful traumatic neuroma, either as a direct cause of neuroma-associated pain or as an indirect marker of local mechanical stimuli, and 2) the presence of alpha-SMA in the painful group may provide rationale for transpositional procedures in the management of traumatic neuroma. The persistent existence of alpha-SMA in the painful group and the correlation with VAS scores may provide insight into the development of new therapeutic strategies.