Plumb Ashley N, Hayashi Kazuhiro, Janowski Adam, Smith Angela, Rasmussen Lynn, Sluka Kathleen A, Lesnak Joseph B
Department of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, IA, USA. Dr. Lesnak is now with University of Texas at Dallas, Department of Neuroscience, Richardson, TX.
Pain Rep. 2024 Nov 20;9(6):e1207. doi: 10.1097/PR9.0000000000001207. eCollection 2024 Dec.
Pregabalin, which acts on the αδ-1 subunit of voltage-gated calcium channels, relieves ≥50% of pain in a third of individuals with fibromyalgia. Thus far, preclinical studies of pregabalin have predominantly used male animals.
The purpose of our study was to investigate potential sex differences in the analgesic efficacy of pregabalin that may contribute to disparities in human outcomes.
We used a mouse model of chronic widespread muscle pain (CWP) to test the effects of pregabalin on muscle hyperalgesia, nonreflexive pain, and motor behaviors. The CWP pain model combines 2 pH 4.0 saline injections, spaced 5 days apart, into the gastrocnemius muscle and produces bilateral muscle hyperalgesia. Furthermore, we explored sex differences in the mRNA and protein expression of the αδ-1 subunit of voltage-gated calcium channels in the dorsal horn of the spinal cord and dorsal root ganglia after development of CWP.
Pregabalin fully attenuated muscle hyperalgesia bilaterally in male but not female mice with equal motor deficits produced in both sexes. In addition, using the conditioned place preference test, mice of both sexes with CWP spent significantly more time in the pregabalin-paired chamber compared with baseline, but not significantly greater than pain-free controls. Chronic widespread muscle pain produced no changes in αδ-1 subunit mRNA or protein expression in the dorsal horn of the spinal cord or dorsal root ganglia in either sex.
Overall, these findings indicate pregabalin may be more effective in treating CWP in males, but the factors leading to these differences are not fully understood.
普瑞巴林作用于电压门控钙通道的αδ-1亚基，可使三分之一的纤维肌痛患者疼痛缓解≥50%。迄今为止，普瑞巴林的临床前研究主要使用雄性动物。
我们研究的目的是调查普瑞巴林镇痛效果中可能导致人类治疗结果差异的潜在性别差异。
我们使用慢性广泛性肌肉疼痛（CWP）小鼠模型来测试普瑞巴林对肌肉痛觉过敏、非反射性疼痛和运动行为的影响。CWP疼痛模型包括在腓肠肌中间隔5天注射两次pH 4.0生理盐水，可产生双侧肌肉痛觉过敏。此外，我们探究了CWP形成后脊髓背角和背根神经节中电压门控钙通道αδ-1亚基的mRNA和蛋白表达的性别差异。
普瑞巴林可完全减轻雄性小鼠双侧的肌肉痛觉过敏，但对雌性小鼠无效，且两性均产生了相同程度的运动缺陷。此外，使用条件性位置偏爱试验，与基线相比，患有CWP的两性小鼠在与普瑞巴林配对的试验箱中停留的时间显著更长，但并不显著长于无疼痛的对照组。慢性广泛性肌肉疼痛并未使两性脊髓背角或背根神经节中的αδ-1亚基mRNA或蛋白表达发生变化。
总体而言，这些发现表明普瑞巴林在治疗男性CWP方面可能更有效，但导致这些差异的因素尚不完全清楚。
