Pain
-
Spinally released dynorphin contributes to hypersensitivity from nerve injury, inflammation, and sustained morphine treatment, but its role in post-operative pain has not been tested. Intrathecal injection of dynorphin activates cyclooxygenase (COX)-1 and -2 to induce hypersensitivity. Spinal COX-1 expression and activity increase following incisional paw surgery in rats, although the stimulus for this increase is not known. ⋯ Spinal cord microglia in culture expressed COX-1 immunoreactivity and released PGE2, but dynorphin A failed to increase release of PGE2 in these cultures. These results suggest that increased COX-1 expression occurs in spinal cord microglia following incisional surgery. Although prodynorphin immunoreactivity also increases, it likely does not drive COX-1 expression or mechanical hypersensitivity in this setting.
-
Mechanisms of chronic pain, including neuropathic pain, are poorly understood. Upregulation of voltage-gated calcium channel (VGCC) alpha2delta1 subunit (Ca(v)alpha2delta1) in sensory neurons and dorsal spinal cord by peripheral nerve injury has been suggested to contribute to neuropathic pain. To investigate the mechanisms without the influence of other injury factors, we have created transgenic mice that constitutively overexpress Ca(v)alpha2delta1 in neuronal tissues. ⋯ In addition, gabapentin blocked VGCC currents concentration-dependently in transgenic, but not wild-type, sensory neurons. Thus, elevated neuronal Ca(v)alpha2delta1 contributes to specific pain states through a mechanism mediated at least partially by enhanced VGCC activity in sensory neurons and hyperexcitability in dorsal horn neurons in response to peripheral stimulation. Modulation of enhanced VGCC activity by gabapentin may underlie at least partially its antihyperalgesic actions.
-
In the spinal dorsal horn, activation of the nicotinic acetylcholine receptors (nAChR) by exogenously applied agonists is known to enhance inhibitory synaptic transmission, and to produce analgesia. However, it is still unknown whether endogenously released acetylcholine exerts a tonic inhibition on nociceptive transmission through the nAChRs in the spinal dorsal horn. Here, we report the presence of such a tonic inhibitory mechanism in the spinal dorsal horn in mice. ⋯ On the other hand, the nicotinic antagonists had no effect on the excitatory postsynaptic currents (EPSCs). Finally, acetylcholine-esterase inhibitor neostigmine-induced facilitation of IPSC frequencies in SG neurons was inhibited by mecamylamine and DHbetaE. Altogether these findings suggest that nicotinic cholinergic system in the spinal dorsal horn can tonically inhibit nociceptive transmission through presynaptic facilitation of inhibitory neurotransmission in SG via the alpha4beta2 subtype of nAChR.
-
Chronic fibromyalgia (FM) pain is prevalent (estimated as high as 13%), predominantly affects women, and is associated with a variety of focal pain conditions. Ongoing FM pain is referred to deep tissues and is described as widespread but usually is maximally located within a restricted region such as the shoulders. Palpation of deep tissues reveals an enhanced nociceptive sensitivity that is not restricted to regions of clinical pain. ⋯ Thus, it appears that central mechanisms of FM pain are dependent on abnormal peripheral input(s) for development and maintenance of this condition. A substantial literature defines peripheral-CNS-peripheral interactions that are integral to FM pain. These reciprocal actions and related phenomena of relevance to FM pain are reviewed here, leading to suggestions for testing of therapeutic approaches.
-
Clinical Trial
The evaluation of acute pain in individuals with cognitive impairment: a differential effect of the level of impairment.
The present study investigated whether the level of cognitive impairment (CI) affects acute pain behavior and how it is manifested. Participants were 159 individuals (mean age 42+/-12), 121 with CI (divided into four groups according to the level of CI: mild, moderate, severe, profound) and 38 with normal cognition (controls). The behavior of the participants before and during acute pain (influenza vaccination) was coded by two raters with the Facial Action Coding System (FACS - scores facial reactions to pain) and the Non-Communicating Children's Pain Checklist (NCCPC-R - scores both facial and general body reactions). ⋯ In contrast, individuals with severe-profound CI exhibited high rates of "freezing reaction" (stillness) during vaccination, manifested mainly in the face and therefore resulting in elevation of only NCCPC-R scores but not of FACS's. The results suggest that the level of CI affects baseline as well as pain behavior and it is therefore necessary to choose an appropriate behavioral tool to measure pain in these individuals accordingly. For example, tools based on facial reactions alone might provide the false impression that individuals with severe-profound CI are insensitive to pain (due to freezing).