School of Medical Sciences (Anatomy and Histology), The University of Sydney, NSW 2006, Australia.
Neuroscience. 2010 Nov 24;171(1):329-43. doi: 10.1016/j.neuroscience.2010.08.040. Epub 2010 Aug 26.
Following unilateral chronic constriction injury (CCI) of the sciatic nerve, histochemical and gene expression changes were examined in the rat nucleus accumbens (NAcc), a region critical to affective-motivational regulation. Rats were categorised as having Pain alone (45%) or Pain and Disability (30%), on the basis of either unaltered or decreased dominance behaviour in the resident-intruder paradigm, respectively. Tyrosine hydroxylase (TH) expression was significantly increased bilaterally, throughout the rostrocaudal extent of the NAcc in Pain alone animals. Increased TH likely reflects increased dopamine levels in the Pain alone group, which may modulate dopamine receptor subtype 2 (D2) receptor expression. Stereological analyses of D2 receptor immunoreactive (D2-IR) cells revealed lateralised changes which correlated significantly with dominance behaviour. In the contralateral NAcc, D2-IR negatively correlated with post-CCI dominance behaviour (i.e. Pain alone animals have decreased D2-IR), whereas ipsilaterally there was a positive correlation between D2-IR and post-CCI dominance behaviour (i.e. Pain and Disability animals have decreased D2-IR). Western blots for D2 protein expression confirmed these correlations. Additionally, D2 mRNA expression within the NAcc showed lateralised and group specific changes. In the ipsilateral NAcc D2 mRNA was increased in Pain alone animals. It is hypothesised that increased D2 mRNA in the ipsilateral NAcc of Pain alone animals may be a protective mechanism, maintaining D2-IR despite increased dopamine, which may otherwise induce receptor desensitisation. D2 mRNA is not altered in the ipsilateral NAcc of Pain and Disability animals, therefore loss of D2-IR is likely, albeit by an alternate mechanism. In summary, unilateral CCI in rats induces specific and lateralised adaptations in the dopaminergic circuitry of the NAcc. These distinct neural adaptations correlate with changes in social behaviour, and likely underlie some of the affective-motivational state changes associated with neuropathic pain in a subset of rats (i.e. Pain and Disability group).
在单侧慢性坐骨神经缩窄损伤(CCI)后,研究人员检查了大鼠伏隔核(NAcc)中的组织化学和基因表达变化,该区域对情感动机调节至关重要。根据在居留者-入侵者范式中行为支配力是否改变或降低,将大鼠分为仅疼痛(45%)或疼痛和残疾(30%)两类。在仅疼痛组中,双侧 NAcc 的整个头尾部,酪氨酸羟化酶(TH)表达显著增加。仅疼痛组中 TH 的增加可能反映了多巴胺水平的升高,这可能调节多巴胺受体亚型 2(D2)受体的表达。D2 受体免疫反应性(D2-IR)细胞的体视学分析显示,侧化变化与支配力行为显著相关。在对侧 NAcc 中,D2-IR 与 CCI 后支配力行为呈负相关(即,仅疼痛组动物 D2-IR 减少),而在同侧,D2-IR 与 CCI 后支配力行为呈正相关(即,疼痛和残疾组动物 D2-IR 减少)。D2 蛋白表达的 Western blot 验证了这些相关性。此外,NAcc 内的 D2 mRNA 表达也显示出侧化和组特异性变化。在仅疼痛组的同侧 NAcc 中,D2 mRNA 增加。研究假设,仅疼痛组大鼠同侧 NAcc 中 D2 mRNA 的增加可能是一种保护机制,尽管多巴胺增加,但仍能维持 D2-IR,否则可能会诱导受体脱敏。疼痛和残疾组大鼠同侧 NAcc 中的 D2 mRNA 没有改变,因此 D2-IR 的丧失很可能发生,尽管是通过另一种机制。总之,CCI 诱导了大鼠 NAcc 中多巴胺能回路的特定和侧化适应性。这些不同的神经适应性与社会行为的变化相关,可能是与神经病理性疼痛相关的一些情感动机状态变化的基础(即疼痛和残疾组)。