Neuroelectrophysiology Multiuser Centre, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil; Laboratory of Neurosciences of Pain & Emotions, Department of Surgery and Anatomy, FMRP-USP, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil.
Neuroelectrophysiology Multiuser Centre, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil; Laboratory of Neurosciences of Pain & Emotions, Department of Surgery and Anatomy, FMRP-USP, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil; Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, FMRP-USP, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil; Behavioural Neurosciences Institute (INeC), Av. do Café, 2450, Monte Alegre, Ribeirão Preto, 14050-220, São Paulo, Brazil.
Brain Res Bull. 2021 Sep;174:323-338. doi: 10.1016/j.brainresbull.2021.06.017. Epub 2021 Jun 27.
The prelimbic division (PrL) of the medial prefrontal cortex (mPFC) is a cerebral division that is putatively implicated in the chronic pain and depression. We investigated the activity of PrL cortex neurons in Wistar rats that underwent chronic constriction injury (CCI) of sciatic nerve and were further subjected to the forced swimming (FS) test and mechanical allodynia (by von Frey test). The effect of blockade of synapses with cobalt chloride (CoCl), and the treatment of the PrL cortex with cannabidiol (CBD), the CB receptor antagonist AM251 and the 5-HT receptor antagonist WAY-100635 were also investigated. Our results showed that CoCl decreased the time spent immobile during the FS test but did not alter mechanical allodynia. CBD (at 15, 30 and 60 nmol) in the PrL cortex also decreased the frequency and duration of immobility; however, only the dose of 30 nmol of CBD attenuated mechanical allodynia in rats with chronic NP. AM251 and WAY-100635 in the PrL cortex attenuated the antidepressive and analgesic effect caused by CBD but did not alter the immobility and the mechanical allodynia when administered alone. These data show that the PrL cortex is part of the neural substrate underlying the comorbidity between NP and depression. Also, the previous blockade of CB cannabinoid receptors and 5-HT serotonergic receptors in the PrL cortex attenuated the antidepressive and analgesics effect of the CBD. They also suggest that CBD could be a potential medicine for the treatment of depressive and pain symptoms in patients with chronic NP/depression comorbidity.
扣带皮层的前额叶皮质（mPFC）的前扣带皮层（PrL）是一个大脑区域，据称它与慢性疼痛和抑郁有关。我们研究了接受坐骨神经慢性缩窄性损伤（CCI）的 Wistar 大鼠的 PrL 皮层神经元的活性，然后对它们进行了强迫游泳（FS）测试和机械性痛觉过敏（von Frey 测试）。还研究了用氯化钴（CoCl）阻断突触、用大麻素受体拮抗剂 CBD、CB 受体拮抗剂 AM251 和 5-HT 受体拮抗剂 WAY-100635 处理 PrL 皮层的效果。我们的结果表明，CoCl 减少了 FS 测试中不动的时间，但没有改变机械性痛觉过敏。PrL 皮层中的 CBD（15、30 和 60 nmol）也减少了不动的频率和持续时间；然而，只有 30 nmol 的 CBD 剂量减轻了慢性 NP 大鼠的机械性痛觉过敏。PrL 皮层中的 AM251 和 WAY-100635 减弱了 CBD 引起的抗抑郁和镇痛作用，但单独给药时不会改变不动和机械性痛觉过敏。这些数据表明，PrL 皮层是 NP 和抑郁共病的神经基础的一部分。此外，先前在 PrL 皮层中阻断 CB 大麻素受体和 5-HT 血清素受体减弱了 CBD 的抗抑郁和镇痛作用。它们还表明，CBD 可能是治疗慢性 NP/抑郁共病患者抑郁和疼痛症状的潜在药物。
