PAIN REGULATORY DYSFUNCTION IN CHRONIC PAIN

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。具体目标1：研究α 2肾上腺素能机制在介导无痛正常血压人群静息血压和急性疼痛敏感性之间的反向关系中的作用。如果α-2肾上腺素能机制有助于反向BP/急性疼痛敏感性关系，则α-2肾上腺素能受体的选择性药理学阻断应显著减弱这种关系。 具体目标二：确定α-2肾上腺素能功能的变化是否有助于静息血压和急性疼痛敏感性之间关系的慢性疼痛相关改变。基于先前的工作，预计慢性疼痛样本将显示相对于无痛对照的BP/急性疼痛敏感性关系的显著改变（逆转）。如果与慢性疼痛相关的α-2肾上腺素能抑制活性受损导致这些改变，则预期存在显著的相互作用，使得α-2阻滞剂将显著减弱无疼痛对照组的BP/疼痛敏感性关系，但对慢性疼痛组的这种关系几乎没有影响。 具体目标3：确定压力感受器敏感性的变化是否有助于改变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的关系。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和无痛对照组的BP/疼痛敏感性改变，则预计自发压力感受器敏感性方差的统计控制将显著减弱BP/疼痛敏感性关系中的组间差异。 具体目标4：确定慢性疼痛相关的疼痛促进通路激活是否有助于改变慢性疼痛患者相对于无痛对照的静息血压和急性疼痛敏感性之间的关系。如果与慢性疼痛相关的中枢伤害性致敏介导慢性疼痛和无痛对照组的BP/疼痛敏感性改变，则预期中枢致敏（时间总和程度）方差的统计控制将显著减弱BP/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.