Pain
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Comparative Study
Spinal NK-1 receptor expressing neurons mediate opioid-induced hyperalgesia and antinociceptive tolerance via activation of descending pathways.
Opioids can induce hyperalgesia in humans and in animals. Mechanisms of opiate-induced hyperalgesia and possibly of spinal antinociceptive tolerance may be linked to pronociceptive adaptations occurring at multiple levels of the nervous system including activation of descending facilitatory influences from the brainstem, spinal neuroplasticity, and changes in primary afferent fibers. Here, the role of NK-1 receptor expressing cells in the spinal dorsal horn in morphine-induced hyperalgesia and spinal antinociceptive tolerance was assessed by ablating these cells with intrathecal injection of SP-saporin (SP-SAP). ⋯ Thus, NK-1 receptor expressing neurons play a critical role in sustained morphine-induced neuroplastic changes which underlie spinal excitability reflected as thermal and tactile hypersensitivity to peripheral stimuli, and to reduced antinociceptive actions of spinal morphine (i.e., antinociceptive tolerance). Ablation of these cells likely eliminates the ascending limb of a spinal-bulbospinal loop that engages descending facilitation and elicits subsequent spinal neuroplasticity. The data may provide a basis for understanding mechanisms of prolonged pain which can occur in the absence of tissue injury.
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Temporal summation of "second pain" (TSSP) is considered to be the result of C-fiber-evoked responses of dorsal horn neurons, termed 'windup'. This phenomenon is dependent on stimulus frequency (0.33 Hz) and relevant for central sensitization and chronic pain. Previous brain imaging studies have only been used to characterize neural correlates of second pain but not its temporal summation. ⋯ As predicted, experimental pain ratings showed robust TSSP during 0.33 Hz but not 0.17 Hz stimuli. fMRI statistical maps identified several brain regions with stimulus and frequency dependent activation consistent with TSSP, including contralateral thalamus (THAL), S1, bilateral S2, anterior and posterior insula (INS), mid-anterior cingulate cortex (ACC), and supplemental motor areas (SMA). TSSP ratings were significantly correlated with brain activation in somatosensory areas (THAL, S1, left S2), anterior INS, and ACC. These results show that neural responses related to TSSP are evoked in somatosensory processing areas (THAL, S2), as well as in multiple areas that serve other functions related to pain, such as cognition (ACC, PFC), affect (INS, ACC, PAG), pre-motor activity (SMA, cerebellum), and pain modulation (rostral ACC).
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Pain that interferes with daily life appears to be strongly age-related in cross-sectional studies, although the nature of this relationship over time has not been established. We have investigated the onset and persistence of pain and pain interference over a 3-year period to determine their association with age in older people. A 3-year follow-up postal survey was conducted of adults aged 50 years and over (n=5366) who had previously been recruited as part of the North Staffordshire Osteoarthritis Project. ⋯ In adults aged 50 years and over, the onset of pain that interferes with life shows a clear gender difference and a consistent rise with age into the oldest age-group. This was in strong contrast to the onset of pain which showed no gender or age-related trends. The implications for public health, as for the treatment of the individual, are twofold, relating to efforts to prevent disabling pain from occurring and to understand the factors that accelerate the impact which pain has on everyday life when people reach the oldest ages.
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Clinical Trial
Ethnic identity predicts experimental pain sensitivity in African Americans and Hispanics.
The aim of this study was to examine experimental pain sensitivity in three ethnic groups, African Americans, Hispanic Americans and non-Hispanic White Americans, and to determine whether ethnic identity is differentially associated with pain sensitivity across ethnic groups. Participants included sixty-three African American, sixty-one Hispanic and eighty-two non-Hispanic white participants who were assessed using three experimental pain measures: thermal, cold-pressor and ischemic. Participants' ethnic identity was assessed using the Multi-group Ethnic Identity Measure (MEIM). ⋯ Statistically controlling for ethnic identity rendered some of the group differences in pain range non-significant. These findings indicate that ethnic identity is associated with pain sensitivity in ethnic minority groups, and may partially mediate group differences in pain perception. The results of the present investigation provide evidence of ethnic group differences in responses to experimental pain across multiple noxious stimuli, with both minority groups exhibiting greater sensitivity to laboratory evoked pain compared to non-Hispanic White Americans.
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Comparative Study
ASIC3 in muscle mediates mechanical, but not heat, hyperalgesia associated with muscle inflammation.
Peripheral initiators of muscle pain are virtually unknown, but likely key to development of chronic pain after muscle insult. The current study tested the hypothesis that ASIC3 in muscle is necessary for development of cutaneous mechanical, but not heat, hyperalgesia induced by muscle inflammation. Using mechanical and heat stimuli, we assessed behavioral responses in ASIC3-/- and ASIC3+/+ mice after induction of carrageenan muscle inflammation. ⋯ Injection of ASIC3-encoding virus into muscle or skin of ASIC3-/- mice resulted in ASIC3 mRNA in DRG and protein expression in DRG and the peripheral injection site. Injection of ASIC3-encoding virus into muscle, but not skin, resulted in development of mechanical hyperalgesia similar to that observed in ASIC3+/+ mice. Thus, ASIC3 in primary afferent fibers innervating muscle is critical to development of hyperalgesia that results from muscle insult.