The spinal biology in humans and animals of pain states generated by persistent small afferent input

Behavioral models indicate that persistent small afferent input, as generated by tissue injury, results in a hyperalgesia at the site of injury and a tactile allodynia in areas adjacent to the injury site. Hyperalgesia reflects a sensitization of the peripheral terminal and a central facilitation evoked by the persistent small afferent input. The allodynia reflects a central sensitization. The spinal pharmacology of these pain states has been defined in the unanesthetized rat prepared with spinal catheters for injection and dialysis. After tissue injury, excitatory transmitters (e.g., glutamate and substance P) acting though N-methyl-d-aspartate (NMDA) and neurokinin 1 receptors initiate a cascade that evokes release of (i) NO, (ii) cyclooxygenase products, and (iii) activation of several kinases. Spinal dialysis show amino acid and prostanoid release after cutaneous injury. Spinal neurokinin 1, NMDA, and non-NMDA receptors enhance spinal prostaglandin E2 release. Spinal prostaglandins facilitate release of spinal amino acids and peptides. Activation by intrathecal injection of receptors on spinal C fiber terminals (μ,/∂ opiate, α2 adrenergic, neuropeptide Y) prevents release of primary afferent peptides and spinal amino acids and blocks acute and facilitated pain states. Conversely, consistent with their role in facilitated processing, NMDA, cyclooxygenase 2, and NO synthase inhibitors act to diminish only hyperalgesia. Importantly, spinal delivery of several of these agents diminishes human injury pain states. This efficacy emphasizes (i) the role of facilitated states in humans, (ii) shows the importance of spinal systems in human pain processing, and (iii) indicates that these preclinical mechanisms reflect processes that regulate the human pain experience.

The genetics of pain and pain inhibition.

The present review summarizes the current state of knowledge about the genetics of pain-related phenomena and illustrates the scope and power of genetic approaches to the study of pain. We focus on work performed in our laboratories in Jastrzebiec, Poland; Portland, OR; and Los Angeles, which we feel demonstrates the continuing usefulness of classical genetic approaches, especially when used in combination with newly available molecular genetic techniques.

The mystery of pain : a book for the sorrowful /

Mode of access: Internet.

Accident avoidance evaluation of General Motors experimental safety vehicle. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Accident avoidance capabilities of mopeds. Volume I: executive summary. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Accident avoidance capabilities of mopeds. Volume II: technical report. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

The gospel of pain,

Mode of access: Internet.

The plain guide to Universalism : designed to lead inquirers to the belief of that doctrine, and believers to the practice of it /

Includes indexes.

The angel of pain.

Mode of access: Internet.

On rest and pain; a course of lectures on the influence of mechanical and physiological rest in the treatment of accidents and surgical diseases, and the diagnostic value of pain.

Second ed. of G/M 2, no. 4791.

Adult attachment, anxiety, and pain self-efficacy as predictors of pain intensity and disability

Pain self-efficacy and anxiety have each been shown to contribute substantially to pain intensity and pain-related disability. Although adult attachment theory has been related separately to chronic pain, anxiety, and self-efficacy, it has not before been investigated with either pain self-efficacy or anxiety in the context of chronic pain. This study investigated the interrelations between these aspects of the chronic pain experience and their relative contributions towards pain intensity and disability. A clinical sample of 152 chronic pain patients participated in this study, completing self-report measures of attachment, self-efficacy, pain intensity, and disability, prior to attending a multidisciplinary pain clinic. Results revealed that fearful and preoccupied (anxious) attachment categories were associated with low pain self-efficacy, while high scores on the attachment dimension of comfort with closeness were linked with high pain self-efficacy, particularly for males. Insecure attachment (whether defined in terms of categories or dimensions) was related to higher levels of anxiety. Pain self-efficacy proved a stronger predictor of pain intensity than did anxiety and was a stronger predictor of disability than pain intensity or anxiety. In addition, comfort with closeness moderated the associations between pain self-efficacy and disability, pain self-efficacy and pain intensity, and anxiety and disability. Together, these findings support the value of adopting an attachment theoretical approach in the context of chronic pain. Treatment considerations and future research directions are considered. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

N-type calcium channel blockers: Novel therapeutics for the treatment of pain

Highly selective Cav2.2 voltage-gated calcium channel (VGCC) inhibitors have emerged as a new class of therapeutics for the treatment of chronic and neuropathic pain. Cone snail venoms provided the first drug in class with FDA approval granted in 2005 to Prialt (ω-conotoxin MVIIA, Elan) for the treatment of neuropathic pain. Since this pioneering work, major efforts underway to develop alternative small molecule inhibitors of Cav2.2 calcium channel have met with varied success. This review focuses on the properties of the Cav2.2 calcium channel in different pain states, the action of ω-conotoxins GVIA, MVIIA and CVID, describing their structure-activity relationships and potential as leads for the design of improved Cav2.2 calcium channel therapeutics, and finally the development of small molecules for the treatment of chronic pain.