Pain
-
The effect of PF-04457845, a potent and selective fatty acid amide hydrolase-1 (FAAH1) inhibitor, on pain due to osteoarthritis of the knee was investigated in a randomised placebo and active-controlled clinical trial. The trial involved 2 periods (separated by a 2-week washout) consisting of a 1-week wash-in phase followed by 2weeks double-blind treatment. Patients received single-blind placebo throughout the wash-in and washout periods. ⋯ PF-04457845 was well tolerated in osteoarthritis patients, and there was no evidence of cannabinoid-type adverse events. The lack of analgesic effect of FAAH1 inhibition in humans is in contrast to data from animal models. This apparent disconnect between species needs further study.
-
Partial nerve injury leads to peripheral neuropathic pain. This injury results in conducting/uninterrupted (also called uninjured)sensory fibres, conducting through the damaged nerve alongside axotomised/degenerating fibres. In rats seven days after L5 spinal nerve axotomy (SNA) or modified-SNA (added loose-ligation of L4 spinal nerve with neuroinflammation-inducing chromic-gut),we investigated (a) neuropathic pain behaviours and (b) electrophysiological changes in conducting/uninterrupted L4 dorsal root ganglion (DRG) neurons with receptive fields (called: L4-receptive-field-neurons). ⋯ We recorded intracellularly in vivo from normal L4/L5 DRG neurons and ipsilateral L4-receptive-field-neurons. After SNA or modified-SNA, L4-receptive-field-neurons showed the following: (a) increased percentages of C-, Aδ-, and Aβ-nociceptors and cutaneous Aα/β-low-thresholdmechanoreceptors with ongoing/spontaneous firing; (b) spontaneous firing in C-nociceptors that originated peripherally; this was ata faster rate in modified-SNA than SNA; (c) decreased electricalthresholds in A-nociceptors after SNA; (d) hyperpolarised membrane potentials in A-nociceptors and Aα/-low-thresholdmechanoreceptors after SNA, but not C-nociceptors; (e) decreased somatic action potential rise times in C- and A-nociceptors, not Aα/β-low-threshold-mechanoreceptors. We suggest that these changes in subtypes of conducting/uninterrupted neurons after partial nerve injury contribute to the different aspects of neuropathic pain as follows: spontaneous firing in nociceptors to ongoing/spontaneous pain; spontaneous firing in Aα/β-low-threshold-mechanoreceptors to dysesthesias/paresthesias; and lowered A-nociceptor electrical thresholds to A-nociceptor sensitization,and greater evoked pain [corrected].
-
Many acute stressors reduce pain, a phenomenon called stress-induced antinociception (SIA). Stress also is associated with increased scratching in chronic itch conditions. We investigated effects of acute stressors on facial itch and pain using a recently introduced rat model. ⋯ W-SIA tended to equalize scratching and swiping elicited by 5-HT and AITC compared with no-swim controls, suggesting altered itch and pain processing. Exercise (wheel-running), novelty, cold exposure, and fear (shaker table), key components of swim stress, differentially affected tail-flick latencies and 5-HT-evoked swiping and scratching behavior. Thus, itch and pain can be simultaneously suppressed by a combination of acute stress-related factors via an opioid-independent mechanism.
-
Depression is a common feature of chronic pain, but there is limited research into the content and frequency of depressed cognitions in pain patients. A limitation of previous research is the failure to include nonpain depressed comparison groups. The present study used a sentence completion task to investigate the content of cognition in 4 groups of participants: with pain and concurrent depression, pain without depression, depression without pain, and with neither pain nor depression. ⋯ The strengths of the current study are the inclusion of the depressed nonpain group, the use of a comprehensive coding scheme applied by 2 independent raters, and the presence of depression validated through a diagnostic interview. In contrast to depressed groups without pain, participants with pain and depression exhibit a cognitive bias specific to negative aspect of health. This focus facilitates understanding of the relationship between depression and pain processing: The implications for therapeutic interventions are discussed.