Diabetic peripheral neuropathic pain (DPNP), the most debilitating complication of diabetes mellitus, is resistant to current therapy. The pathogenesis of DPNP is still elusive, but several mechanisms have been proposed including abnormal hyperexcitability of dorsal root ganglion (DRG) neurons. The underlying molecular mechanisms of such aberrant hyperexcitability are incompletely understood. Using the streptozotocin (STZ) rat model of DPNP, we have recently provided evidence implicating neuronal K_v7 channels that normally exert a powerful stabilizing influence on neuronal excitability, in the abnormal hyperexcitability of DRG neurons and in pain hypersensitivity associated with DPNP. In the present immunohistochemical study, we sought to determine whether K_v7.2 and/or K_v7.5 channel expression is altered in DRG neurons in STZ rats. We found 35 days post-STZ: (1) a significant decrease in K_v7.5-immunoreactivity in small (<30 μm) DRG neurons (both IB4 positive and IB4 negative) and medium-sized (30−40 μm) neurons, and (2) a significant increase in K_v7.2-immunoreactivity in small (<30 μm) neurons, and a non-significant increase in medium/large neurons. The decrease in K_v7.5 channel expression in small and medium-sized DRG neurons in STZ rats is likely to contribute to the mechanisms of hyperexcitability of these neurons and thereby to the resulting pain hypersensitivity associated with DPNP. The upregulation of K_v7.2 subunit in small DRG neurons may be an activity dependent compensatory mechanism to limit STZ-induced hyperexcitability of DRG neurons and the associated pain hypersensitivity. The findings support the notion that K_v7 channels may represent a novel target for DPNP treatment.

糖尿病性周围神经性疼痛（DPNP）是糖尿病中最使人衰弱的并发症，对目前的治疗有抵抗力。DPNP的发病机制仍然难以捉摸，但是已经提出了几种机制，包括背根神经节（DRG）神经元的异常过度兴奋。这种异常过度兴奋的潜在分子机制尚未完全理解。使用DPNP的链脲佐菌素（STZ）大鼠模型，我们最近提供了证据，证明神经元K _v 7通道通常对神经元兴奋性，DRG神经元的异常超兴奋性以及与DPNP相关的疼痛超敏反应具有强大的稳定作用。在目前的免疫组化研究中，我们试图确定K _v 7.2和/或K _v7.5通道表达在STZ大鼠的DRG神经元中改变。我们发现STZ后35天：（1）小（<30μm）DRG神经元（IB4阳性和IB4阴性）和中型（30-40μm）神经元的K _v 7.5免疫反应显着降低，并且（2）小（<30μm）神经元的K _v 7.2免疫反应性显着增加，中/大神经元无显着增加。STZ大鼠中小DRG神经元中K _v 7.5通道表达的减少可能有助于这些神经元的过度兴奋性机制，从而导致与DPNP相关的疼痛超敏反应。K _v的上调7.2小DRG神经元中的亚基可能是一种依赖于活动的补偿机制，以限制STZ诱导的DRG神经元过度兴奋和相关的疼痛超敏反应。这些发现支持了K _v 7通道可能代表DPNP治疗的新靶标这一观点。