PAIN REGULATORY DYSFUNCTION IN CHRONIC PAIN

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。特异性目的1：研究α -2肾上腺素能机制在无痛正常血压人群中介导静息血压与急性疼痛敏感性之间的负相关关系中的作用。如果α -2肾上腺素能机制有助于逆血压/急性疼痛敏感性的关系，α -2肾上腺素能受体的选择性药物阻断应该显著减弱这种关系。特异性目的2：确定α -2肾上腺素能功能的改变是否有助于静息血压与急性疼痛敏感性之间的慢性疼痛相关改变。基于先前的工作，预计慢性疼痛样本相对于无痛对照，在BP/急性疼痛敏感性关系中会显示出显著的改变（逆转）。如果与慢性疼痛相关的α -2肾上腺素能抑制活性的损害导致了这些改变，那么预计α -2阻断会显著减弱无痛对照组的血压/疼痛敏感性关系，但对慢性疼痛组的这种关系影响不大。特异性目的3：确定相对于无痛对照，压力感受器敏感性的变化是否有助于慢性疼痛患者静息血压和急性疼痛敏感性之间关系的改变。如果与慢性疼痛相关的压力感受器敏感性降低介导了慢性疼痛组和无痛对照组之间血压/疼痛敏感性的改变，那么预计自发压力感受器敏感性差异的统计控制将大大减弱血压/疼痛敏感性关系的组间差异。特异性目的4：确定慢性疼痛相关的疼痛促进通路的激活是否有助于慢性疼痛患者相对于无痛对照组的静息血压和急性疼痛敏感性之间关系的改变。如果与慢性疼痛相关的中枢性伤害知觉敏化介导了慢性疼痛和无疼痛对照组的血压/疼痛敏感性改变，那么预计中枢性敏化（时间累加度）方差的统计控制将大大减弱血压/疼痛敏感性关系的组间差异。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aim 1: To examine the role of alpha-2 adrenergic mechanisms in mediating the inverse relationship between resting BP and acute pain sensitivity in pain-free normotensive humans. If alpha-2 adrenergic mechanisms contribute to the inverse BP/acute pain sensitivity relationship, selective pharmacological blockade of alpha-2 adrenergic receptors should significantly attenuate this relationship. Specific Aim 2: To determine whether changes in alpha-2 adrenergic function contribute to chronic pain-related alterations in the relationship between resting BP and acute pain sensitivity. Based on prior work, it is expected that the chronic pain sample will display significant alterations (reversal) in the BP/acute pain sensitivity relationship relative to pain-free controls. If impairments in alpha-2 adrenergic inhibitory activity associated with chronic pain contribute to these alterations, a significant interaction is expected such that alpha-2 blockade will significantly attenuate the BP/pain sensitivity relationship in pain-free controls, but will have little effect on this relationship in the chronic pain group. Specific Aim 3: To determine whether changes in baroreceptor sensitivity contribute to alterations in the relationship between resting BP and acute pain sensitivity in chronic pain patients relative to pain-free controls. If diminished baroreceptor sensitivity associated with chronic pain mediates the BP/pain sensitivity alterations across chronic pain and pain-free control groups, it is expected that statistical control of spontaneous baroreceptor sensitivity variance will substantially attenuate between-group differences in the BP/pain sensitivity relationship. Specific Aim 4: To determine whether chronic pain-related activation of pain facilatory pathways contributes to alterations in the relationship between resting BP and acute pain sensitivity in chronic pain patients relative to pain-free controls. If central nociceptive sensitization associated with chronic pain mediates the BP/pain sensitivity alterations across chronic pain and pain-free control groups, it is expected that statistical control of central sensitization (degree of temporal summation) variance will substantially attenuate between-group differences in the BP/pain sensitivity relationship.