Pain
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Sex differences in endogenous pain modulation were tested in healthy volunteers (32 men, 30 women). Painful contact heat stimuli were delivered to the right leg alone, and then in combination with various electrical conditioning stimuli delivered to the left forearm. Four conditioning protocols were applied to each subject in separate sessions: mild, non-painful (control); distracting; stressful-yet-non-painful; strongly painful. ⋯ Regression analysis revealed that the magnitude of pain-evoked hypoalgesia was predicted by the perceived distraction (p=0.003) and stress (p=0.04) produced by the painful conditioning stimulation, providing evidence that distraction and stress contribute to pain-evoked hypoalgesia. However, the contribution of stress to pain-evoked hypoalgesia differed by sex (p=0.02), with greater perceived stress associated with greater hypoalgesia in men and the opposite trend in women, suggesting sex differences in the mechanisms underlying pain-evoked hypoalgesia. This study provides indirect evidence that multiple neural mechanisms are involved in endogenous pain modulation and suggests that sex-specific aspects of these systems may contribute to greater pain sensitivity and higher prevalence of many chronic pain conditions among women.
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CGRP receptor activation has been implicated in peripheral and central sensitization. The role of spinal CGRP receptors in supraspinal pain processing and higher integrated pain behavior is not known. Here we studied the effect of spinal inhibition of CGRP1 receptors on supraspinally organized vocalizations and activity of amygdala neurons. ⋯ In arthritic rats, the antagonists also inhibited the audible and ultrasonic components of vocalizations evoked by noxious stimuli and increased the threshold of hindlimb withdrawal reflexes. The antagonists had no effect on vocalizations and spinal reflexes in normal rats. These data suggest that spinal CGRP1 receptors are not only important for spinal pain mechanisms but also contribute significantly to the transmission of nociceptive information to the amygdala and to higher integrated behavior.
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Understanding the role of voltage-gated sodium channels in nociception may provide important insights into pain mechanisms. Voltage-gated sodium channels are critically important for electrogenesis and nerve impulse conduction, and a target for important clinically relevant analgesics such as lidocaine. Furthermore, within the last decade studies have shown that certain sodium channel isoforms are predominantly expressed in peripheral sensory neurons associated with pain sensation, and that the expression and functional properties of voltage-gated sodium channels in peripheral sensory neurons can be dynamically regulated following axonal injury or peripheral inflammation. ⋯ Electrophysiological experiments indicate that these pain-associated mutations cause small yet significant changes in the gating properties of voltage-gated sodium channels that are likely to contribute substantially to the development of chronic pain. Equally exciting, recent studies indicate that recessive mutations in Na(v)1.7 that eliminate functional current can result in an apparent complete, and possibly specific, indifference to pain in humans, suggesting that isoform specific blockers could be very effective in treating pain. In this review we will examine what is known about the roles of voltage-gated sodium channels in nociception.
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Comparative Study
The impact of chronic low back pain on older adults: a comparative study of patients and controls.
Chronic low back pain (CLBP) is one of the most common, poorly understood, and potentially disabling chronic pain conditions from which older adults suffer. Many older adults remain quite functional despite CLBP, and because age-related comorbidities often exist independently of pain (e.g., medical illnesses, sleep disturbance, mobility difficulty), the unique impact of CLBP is unknown. We conducted this research to identify the multidimensional factors that distinguish independent community dwelling older adults with CLBP from those that are pain-free. ⋯ Significant differences were ascertained for all 22 measures. Discriminant function analysis revealed that eight measures uniquely maximized the separation between the two groups (self-reported function with the Functional Status Index and the SF-36, performance-based function with repetitive trunk rotation and functional reach, mood with the Geriatric Depression Scale, comorbidity with the Cumulative Illness Rating Scale and BMI, and severity of degenerative disc disease). These results should help to guide investigators that perform studies of CLBP in older adults and practitioners that want an easily adaptable battery for use in clinical settings.