Pain
-
We report a novel symptom in many patients with low back pain (LBP) that sheds new light on the underlying pain mechanism. By means of quantitative sensory testing, we compared patients with radicular LBP (sciatica), axial LBP (LBP without radiation into the leg), and healthy controls, searching for cutaneous allodynia in response to weak tactile and cooling stimuli on the leg and low back. Most patients with radicular pain (~60%) reported static and dynamic tactile allodynia, as well as cooling allodynia, on the leg, often extending into the foot. ⋯ The presence of central sensitization also provides the first cogent account of shooting pain in sciatica as a wave of activity sweeping vectorially across the width of the sensitized dorsal horn. Finally, the results endorse leg allodynia as a pain biomarker in animal research on LBP, which is commonly used but has not been previously validated. In addition to informing the underlying mechanism of LBP, bedside mapping of allodynia might have practical implications for prognosis and treatment.
-
Chemotherapy-induced peripheral neuropathy accompanied by chronic neuropathic pain is the major dose-limiting toxicity of several anticancer agents including the taxane paclitaxel (Taxol). A critical mechanism underlying paclitaxel-induced neuropathic pain is the increased production of peroxynitrite in spinal cord generated in response to activation of the superoxide-generating enzyme, NADPH oxidase. Peroxynitrite in turn contributes to the development of neuropathic pain by modulating several redox-dependent events in spinal cord. ⋯ The first relies on inhibition of the redox-sensitive transcription factor (NFκB) and mitogen activated protein kinases (ERK and p38) resulting in decreased production of neuroexcitatory/proinflammatory cytokines (TNF-α, IL-1β) and increased formation of the neuroprotective/anti-inflammatory IL-10. The second involves inhibition of redox-mediated posttranslational tyrosine nitration and modification (inactivation) of glia-restricted proteins known to play key roles in regulating synaptic glutamate homeostasis: the glutamate transporter GLT-1 and glutamine synthetase. Our results unravel a mechanistic link into biomolecular signaling pathways employed by A3AR activation in neuropathic pain while providing the foundation to consider use of A3AR agonists as therapeutic agents in patients with chemotherapy-induced peripheral neuropathy.
-
Research on placebo analgesia and nocebo hyperalgesia has primarily included healthy subjects or acute pain patients, and it is unknown whether these effects can be obtained in ongoing pain in patients with chronic pain caused by an identifiable nerve injury. Eighteen patients with postthoracotomy neuropathic pain were exposed to placebo and nocebo manipulations, in which they received open and hidden administrations of pain-relieving (lidocaine) or pain-inducing (capsaicin) treatment controlled for the natural history of pain. Immediately after the open administration, patients rated their expected pain levels on a mechanical visual analogue scale (M-VAS). ⋯ Pain increases during nocebo were nonsignificant (P=.394 to 1.000). To our knowledge, this is the first study to demonstrate placebo effects in ongoing neuropathic pain. It provides further evidence for placebo-induced reduction in hyperalgesia and suggests that patients' expectations coexist with emotional feelings about treatments.
-
This study investigated the social judgments that are made about people who appear to be in pain. Fifty-six participants viewed 2 video clips of human figures exercising. The videos were created by a motion tracking system, and showed dots that had been placed at various points on the body, so that body motion was the only visible cue. ⋯ As well as judging them to be in more pain, participants evaluated the person who displayed pain behavior as less warm and less competent than the person who did not display pain behavior. In addition, the person who displayed pain behavior was perceived to be in a more negative mood and to have poorer physical fitness than the person who did not, and these perceptions contributed to the impact of pain behaviors on evaluations of warmth and competence, respectively. The implications of these negative social evaluations for social relationships, well-being, and pain assessment in persons in chronic pain are discussed.
-
Relationships between the paradoxical painful and non painful sensations induced by a thermal grill.
The simultaneous application of innocuous cutaneous warm and cold stimuli with a thermal grill can induce both paradoxical pain and paradoxical warmth (heat). The goal of this study was to investigate further the relationships between these paradoxical sensations. Stimuli were applied to the palms of the right hands of 21 volunteers with a thermode consisting of 6 bars, the temperature of which was controlled by Peltier elements. ⋯ The intensities of the warmth and unpleasantness evoked by the stimuli were directly related to the magnitude of the warm-cold differential. Our results suggest that there is a continuum between the painful and nonpainful paradoxical sensations evoked by the thermal grill that may share pathophysiological mechanisms. These data also confirm the existence of strong relationships between the thermoreceptive and nociceptive systems and the utility of the thermal grill for investigating these relationships.