Pain
-
Recent studies indicate that aging is associated with dysfunctional changes in pain modulatory capacity, potentially contributing to increased incidence of pain in older adults. However, age-related changes in offset analgesia (offset), a form of temporal pain inhibition, remain poorly characterized. The purpose of this study was to investigate age differences in offset analgesia of heat pain in healthy younger and older adults. ⋯ Interestingly, offset analgesia was nonexistent on the palm for all subjects. The reduced offset found in older adults may reflect an age-related decline in endogenous inhibitory systems. However, although the exact mechanisms underlying offset remain unknown, the absence of offset at the palm suggests that peripheral mechanisms may be involved in initiating this phenomenon.
-
The clinical effects of motor cortex stimulation (MCS) for neuropathic pain (NP) is thought to be mediated primarily by the secretion of endogenous opioids in humans and in animal models. Because opioid receptor density is itself decreased in patients with NP, we investigated whether the magnitude and distribution of the remaining opioid receptors in patients with NP could be biological predictors of the pain-relieving effects of MCS. Using (11)C-diprenorphine positron emission tomography scans, opioid receptor availability was assessed in 15 patients suffering refractory NP, who subsequently received chronically implanted MCS. ⋯ The levels of preoperative opioid-binding in the insula, thalamus, periaqueductal gray, anterior cingulate, and orbitofrontal cortex were significantly and positively correlated with postoperative pain relief at 7mo. Patients with receptor density values below the lower limits in age-matched controls in the thalamus, periaqueductal gray and contralateral insula were the least likely to benefit from MCS. Opioid-receptor availability as shown in preoperative positron emission tomography scans appears to be related to the efficacy of MCS in NP and may help clinicians to select the candidates most likely to benefit from this procedure.
-
In the spinal nerve ligation (SNL) model of neuropathic pain, synaptic plasticity shifts the excitation/inhibition balance toward excitation in the spinal dorsal horn. We investigated the deregulation of the synaptogenic neuroligin (NL) molecules, whose NL1 and NL2 isoforms are primarily encountered at excitatory and inhibitory synapses, respectively. In the dorsal horn of SNL rats, NL2 was overexpressed whereas NL1 remained unchanged. ⋯ Expression of the inhibitory scaffolding protein gephyrin remained unchanged, indicating a partial change in NL2 postsynaptic partners in SNL rats. This phenomenon appears to be specific to the NL2(-) isoform. Our data showed unexpected upregulation and pronociceptive effects of the "inhibitory" NL2 in neuropathic pain, suggesting a functional shift of NL2 from inhibition to excitation that changed the synaptic ratio toward higher excitation.
-
The expression of pain is altered in people with dementia (PWD), increasing the risk of undertreatment in that population. The objective of this study was to determine whether dementia and the absence of pain assessment in the patients' medical chart reduced the probability of analgesic use in a large sample of nursing home (NH) residents. This is a cross-sectional study using data from 6275 residents (mean age 86 ± 8.2 years; 73.7% women) from 175 NHs located in France. ⋯ Results remained fairly unchanged after performing several sensitivity analyses. Our results suggest that improvements are needed in pain management in NHs, particularly for PWD. Implementing systematic evaluations of pain in NHs' routine would contribute to a better management of pain, which can lead to important benefits for residents.
-
One feature of neuropathic pain is a reduced spinal gamma-aminobutyric acid (GABA)-ergic inhibitory function. However, the mechanisms behind this attenuation remain to be elucidated. This study investigated the involvement of reactive oxygen species in the spinal GABA neuron loss and reduced GABA neuron excitability in spinal nerve ligation (SNL) model of neuropathic pain in mice. ⋯ Repeated antioxidant treatments significantly reduced the pain behaviors and prevented the reduction in EGFP+ GABA neurons. The response rate of the tonic firing GABA neurons recorded from SNL mice increased with antioxidant treatment, whereas no change was seen in those recorded from naïve mice, which suggested that oxidative stress impaired some spinal GABA neuron activity in the neuropathic pain condition. Together the data suggest that neuropathic pain, at least partially, is attributed to oxidative stress, which induces both a GABA neuron loss and dysfunction of surviving GABA neurons.