Pain
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Randomized Controlled Trial
Reactive oxygen species contribute to neuropathic pain and locomotor dysfunction via activation of CamKII in remote segments following spinal cord contusion injury in rats.
In this study, we examined whether blocking spinal cord injury (SCI)-induced increases in reactive oxygen species (ROS) by a ROS scavenger would attenuate below-level central neuropathic pain and promote recovery of locomotion. Rats with T10 SCI developed mechanical allodynia in both hind paws and overproduction of ROS, as assayed by Dhet intensity, in neurons in the lumbar 4/5 dorsal horn ((∗)P<0.05). To scavenge ROS, phenyl-N-tert-butylnitrone (PBN, a ROS scavenger) was administered immediately after SCI and for 7 consecutive days (early treatment) by either intrathecal (it; 1 and 3mg) or systemic (ip; 10, 50 and 100mg) injections. ⋯ Both SCI and t-BOOH treatment groups showed significantly increased phospho-CamKII (pCamKII) expression in neurons and KN-93 (an inhibitor of pCamKII) significantly attenuated mechanical allodynia ((∗)P<0.05). In addition, high doses of PBN significantly promoted the recovery of locomotion ((∗)P<0.05). In conclusion, the present data suggest that overproduction of ROS contribute to sensory and motor abnormalities in remote segments below the lesion after thoracic SCI.
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Cold allodynia, pain in response to cooling, occurs during or within hours of oxaliplatin infusion and is thought to arise from a direct effect of oxaliplatin on peripheral sensory neurons. To characterize the pathophysiological mechanisms underlying acute oxaliplatin-induced cold allodynia, we established a new intraplantar oxaliplatin mouse model that rapidly developed long-lasting cold allodynia mediated entirely through tetrodotoxin-sensitive Nav pathways. ⋯ Intraplantar injection of the Nav1.6 activator Cn2 elicited spontaneous pain, mechanical allodynia, and enhanced 4-aminopyridine-induced cold allodynia. These findings provide behavioural evidence for a crucial role of Nav1.6 in multiple peripheral pain pathways including cold allodynia.
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The period between migraine attacks is characterized by paradoxical responses to repetitive sensory and transcranial magnetic stimulation (TMS). Abnormal long-term cortical functional plasticity may play a role and can be assessed experimentally by paired associative stimulation (PAS), in which somatosensory peripheral nerve stimuli are followed by TMS of the motor cortex. Changes in motor-evoked potential (MEP) amplitudes were recorded in 16 migraine without aura patients (MO) and 15 healthy volunteers (HV) before and after PAS, which consisted of 90 peripheral electrical right ulnar nerve stimulations and subsequent TMS pulses over the first dorsal interosseous (FDI) muscle activation site with a delay of 10 ms (excitability depressing) or 25 ms (excitability enhancing). ⋯ Although in HV MEP amplitudes were significantly potentiated (+55.1) after PAS25, only a slight, nonsignificant increase was observed in MO (+18.8%). In the control experiment, performed on 8 subjects pooled together, Pearson's correlation showed an inverse relationship between the percentage of MEP amplitude changes after PAS10 and early HFO amplitudes (r=-0.81; P=.01). Because we observed that the more deficient the long-term PAS-induced change, the more the thalamocortical activation decreased, we hypothesize that the abnormalities in long-term cortical plasticity observed in the interictal period between migraine episodes could be due to altered thalamic control.
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Randomized Controlled Trial Multicenter Study
Endogenous opioid function mediates the association between laboratory-evoked pain sensitivity and morphine analgesic responses.
Predictors of responsiveness to opioid analgesic medications are not well understood. This study tested whether individual differences in endogenous opioid (EO) function are associated with analgesic responsiveness to morphine. In randomized, counterbalanced order over 3 sessions, 45 chronic low back pain participants and 31 healthy controls received an opioid antagonist (8 mg naloxone), morphine (0.08 mg/kg), or placebo. ⋯ These latter associations were significantly mediated by EO function for 4 of these 5 pain outcomes (all P values<0.05). In the laboratory-evoked pain context, opioid analgesic medications may supplement inadequate EO analgesia, with little incremental benefit in those with preexisting high EO function. Implications for personalized medicine are discussed.
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Children born very preterm (≤ 32 weeks gestation) exhibit greater internalizing (anxious/depressed) behaviors compared to term-born peers as early as 2 years corrected age (CA); however, the role of early stress in the etiology of internalizing problems in preterm children remains unknown. Therefore, we examined the relationship between neonatal pain and internalizing behavior at 18 months CA in children born very preterm and examined whether parent behavior and stress moderated this relationship. Participants were 145 children (96 very preterm, 49 full term) assessed at 18 months CA. ⋯ Parent Sensitivity and Nonhostility moderated the relationship between neonatal pain and Internalizing behavior (all P<.05); higher parent education (P<.03), lower Parenting Stress (P=.001), and fewer children in the home (P<.01) were associated with lower Internalizing behavior in very preterm children, after adjusting for neonatal medical confounders, gender, and child cognitive ability (all P>.05). Parent Emotional Availability and stress were not associated with Internalizing behaviors in full-term control children. Positive parent interaction and lower stress appears to ameliorate negative effects of neonatal pain on stress-sensitive behaviors in this vulnerable population.