Pain Regulatory Dysfunction in Chronic Pain

描述（由申请人提供）：越来越多的人认识到内源性疼痛调节系统功能障碍可能在慢性疼痛中发挥作用。内源性疼痛调节过程的一个重要组成部分是心血管和疼痛调节系统之间的功能相互作用，这导致静息血压（BP）和急性疼痛敏感性之间的反比关系。这种反向BP/疼痛敏感性关系被认为反映了自适应稳态反馈回路，其有助于在存在疼痛刺激的情况下恢复唤醒水平。反向BP/急性疼痛敏感性关系似乎显著改变（即，在慢性疼痛患者中逆转。有人建议，这些变化反映了慢性疼痛相关的功能障碍，在正常的疼痛调节过程。拟议项目的总体目标是确定可能解释慢性疼痛患者BP/疼痛敏感性关系变化的潜在机制。在无痛血压正常者中，压力感受器介导的机制和α-2肾上腺素能下行疼痛抑制通路似乎可能有助于表达反向血液疼痛敏感性关系。假设慢性疼痛相关的压力感受器敏感性降低和/或肾上腺素能疼痛抑制通路受损介导慢性疼痛患者血压/疼痛敏感性关系的改变。可能与血压调节相互作用的下行疼痛促进通路（中枢致敏）的慢性疼痛相关激活也可能导致这种改变的BP/疼痛敏感性关系。确定负责慢性疼痛相关的BP/疼痛敏感性关系的改变的机制将有助于改善慢性疼痛中功能失调的疼痛调节过程的作用的理解。60名慢性腰痛患者和60名无痛对照者将参加两次实验室检查，一次是用育亨宾进行α-2肾上腺素能阻滞，一次是安慰剂。在每个阶段期间，将测定静息血液和自发压力感受器敏感性，将确定中枢致敏程度（反映在时间总和中），并将评估对急性指压的敏感性、化学性和热痛刺激。从本方案中获得的数据将用于确定：1）α-2肾上腺素能机制在无痛正常血压者中对反向BP/急性疼痛敏感性关系的贡献程度，2）α-2肾上腺素能抑制通路中的慢性疼痛相关损伤是否在慢性疼痛/无痛组中对血压/急性疼痛敏感性关系的改变做出贡献，3）压力感受器敏感性的变化是否有助于BP/疼痛敏感性关系中的慢性疼痛相关改变，以及4）疼痛促进通路的慢性激活是否有助于BP/疼痛敏感性关系中的改变。

DESCRIPTION (provided by applicant): It has been increasingly recognized that dysfunction in endogenous pain regulatory systems may play a role in chronic pain. An important component of the endogenous pain regulatory process is the functional interaction between the cardiovascular and pain regulatory systems, which results in an inverse relationship between resting blood pressure (BP) and acute pain sensitivity. This inverse BP/pain sensitivity relationship is believed to reflect an adaptive homeostatic feedback loop that helps restore arousal levels in the presence of painful stimuli. The inverse BP/acute pain sensitivity relationship appears to be significantly altered (i.e., reversed) in chronic pain patients. It is proposed that these alterations reflect chronic pain-related dysfunction in normal pain regulatory processes. The overall objective of the proposed project is to identify underlying mechanisms that may account for these alterations in the BP/pain sensitivity relationship in chronic pain sufferers. In pain-free normotensives, baroreceptor-mediated mechanisms and alpha-2 adrenergic descending pain inhibitory pathways appear likely to contribute to expression of the inverse blood pain sensitivity relationship. Chronic pain-related decreases in baroreceptor sensitivity and/or impairments in adrenergic pain inhibitory pathways are hypothesized to mediate the altered blood pressure/pain sensitivity relationship in chronic pain sufferers. Chronic pain-related activation of descending pain facilatory pathways (central sensitization) that may interact with blood pressure regulation could also contribute to this altered BP/pain sensitivity relationship. Identifying the mechanisms responsible for chronic pain-related alterations in the BP/pain sensitivity relationship will contribute to improved understanding of the role of dysfunctional pain regulatory processes in chronic pain. Sixty chronic low back pain patients and 60 pain-free controls will participate in two laboratory sessions, once under alpha-2 adrenergic blockade with yohimbine and once under placebo. During each session, resting blood and spontaneous baroreceptor sensitivity will be determined, degree of central sensitization will be ascertained (reflected in temporal summation), and sensitivity to acute finger pressure, is chemic, and heat pain stimuli will be assessed. Data obtained from this protocol will be used to determine: 1) the extent to which alpha-2 adrenergic mechanisms contribute to the inverse BP/acute pain sensitivity relationship in pain-free normotensives,2) whether chronic pain-related impairments in alpha-2 adrenergio inhibitory pathways contribute to alterations in the blood pressure/acute pain sensitivity relationship across chronicpain/pain-free groups, 3) whether changes in baroreceptor sensitivity contribute to chronic pain-related alterations in the BP/pain sensitivity relationship, and 4) whether chronic activation of pain facilatory pathways contributes to alterations in the BP/pain sensitivity relationship.