Pain
-
While group 1 metabotropic glutamate receptors (mGluRs) and ionotropic N-methyl-d-aspartate (NMDA) receptors regulate nociception, the precise molecular mechanism(s) contributing to glutamate signaling in chronic pain remain unclear. Here we not only confirmed the key involvement of Homer proteins in neuropathic pain, but also distinguished between the functional roles for different Homer family members and isoforms. Chronic constriction injury (CCI) of the sciatic nerve induced long-lasting, time-dependent increases in the postsynaptic density expression of the constitutively expressed (CC) isoforms Homer1b/c and/or Homer2a/b in the spinal dorsal horn and supraspinal structures involved in nociception (prefrontal cortex, thalamus), that co-occurred with increases in their associated mGluRs, NR2 subunits of the NMDA receptor, and the activation of downstream kinases. ⋯ Thus, nerve injury-induced increases in CC-Homers expression promote pain in pathological states, but IEG-Homer induction protects against both the development and maintenance of neuropathy. Additionally, exacerbated pain hypersensitivity in transgenic mice with reduced Homer binding to mGluR5 supports also an inhibitory role for Homer interactions with mGluR5 in mediating neuropathy. Such data indicate that nerve injury-induced changes in glutamate receptor/Homer signaling contribute in dynamic but distinct ways to neuropathic pain processing, which has relevance for the etiology of chronic pain symptoms and its treatment.
-
Randomized Controlled Trial
Longstanding neuropathic pain after spinal cord injury is refractory to transcranial direct current stimulation: A randomized controlled trial.
Neuropathic pain remains one of the most difficult consequences of spinal cord injury (SCI) to manage. It is a major cause of suffering and adds to the physical, emotional, and societal impact of the injury. Despite the use of the best available treatments, two thirds of people experiencing neuropathic pain after SCI do not achieve satisfactory pain relief. ⋯ A similar lack of effect was also seen after sham treatment. Because the injury duration in this study was significantly greater than that of previous investigations, it is possible that tDCS is an effective analgesic only in individuals with relatively recent injuries and pain. Future investigations comparing a range of injury durations are required if we are to determine whether this is indeed the case.
-
Randomized Controlled Trial
Lack of endogenous opioid release during sustained visceral pain: A [(11)C]carfentanil PET study.
Opioidergic neurotransmission in the central nervous system is involved in somatic pain, but its role in visceral pain remains unknown. We aimed to quantify endogenous opioid release in the brain during sustained painful gastric distension. Therefore, 2 dynamic [11C]carfentanil positron emission tomography scans were performed in 20 healthy subjects during 2 conditions: sustained (20 minutes) painful proximal gastric balloon distension at predetermined individual discomfort threshold (PAIN) and no distension (NO PAIN), in counterbalanced order. ⋯ No difference in endogenous opioid release was demonstrated in any of the volumes of interest. Thus, contrary to its somatic counterpart, no opioid release is detected in the brain during sustained visceral pain, despite similar pain intensities. Endogenous opioids may play a less important role in visceral compared to somatic pain.
-
The current study applied a model of pain communication to examine the distinction between verbal and nonverbal pain expression in their prediction of punishing, empathic, and solicitous spouse responses to patient pain. It was hypothesized that on days when patients engaged in more nonverbal expression, spouses would respond more positively (ie, with less punishing and more solicitous and empathic behavior). The same pattern was predicted for verbal expression. ⋯ The predicted positive main effect of nonverbal expression on empathic and solicitous responses was supported by the data, as was the positive main effect for verbal pain expression. Results from moderation analyses partially supported our hypothesis in that patients' nonverbal pain expression was even more strongly related to empathic and solicitous spouse responses on days of high verbal pain expression, and patients were buffered from spouse punishing responses on days when both nonverbal and verbal expression were high. These findings suggest that pain expression in both verbal and nonverbal modes of communication is important for positive and negative spousal responses.