Articles: hyperalgesia.
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Sickle cell disease (SCD) is associated with both acute vaso-occlusive painful events as well as chronic pain syndromes, including heightened sensitivity to touch. We have previously shown that mice with severe SCD (HbSS mice; express 100% human sickle hemoglobin in red blood cells; RBCs) have sensitized nociceptors, which contribute to increased mechanical sensitivity. Yet, the hypersensitivity in these neural populations alone may not fully explain the mechanical allodynia phenotype in mouse and humans. ⋯ These novel findings demonstrate mice with severe SCD exhibit mechanical allodynia to both punctate and dynamic light touch and suggest that this behavioral phenotype may be mediated in part by the sensitization of light touch cutaneous afferent fibers to suprathreshold force. These findings indicate that Aβ fibers can be sensitized to mechanical force and should potentially be examined for sensitization in other tissue injury and disease models.
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Frontiers in physiology · Jan 2012
Development of inflammation-induced hyperalgesia and allodynia is associated with the upregulation of extrasynaptic AMPA receptors in tonically firing lamina II dorsal horn neurons.
Persistent peripheral inflammation changes AMPA receptor (AMPAR) trafficking in dorsal horn neurons by promoting internalization of GluR2-containing, Ca(2+)-impermeable AMPARs from the synapses and by increasing insertion of GluR1-containing, Ca(2+)-permeable AMPARs in extrasynaptic plasma membrane. These changes contribute to the maintenance of persistent inflammatory pain. However, much less is known about AMPAR trafficking during development of persistent inflammatory pain and direct studies of extrasynaptic AMPARs functioning during this period are still lacking. ⋯ This upregulation was manifested as a robust increase in the amplitude of AMPAR-mediated currents 2-3 h post-CFA. These changes were observed specifically in SG neurons characterized by intrinsic tonic firing properties, but not in those that exhibited strong adaptation. Our results indicate that CFA-induced inflammation increases functional expression of extrasynaptic AMPARs in tonically firing SG neurons during development of pain hypersensitivity and that this increase may contribute to the development of peripheral persistent pain.
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Inflammation is a part of the body's natural response to tissue injury which initiates the healing process. Unfortunately, inflammation is frequently painful and leads to hypersensitivity to mechanical stimuli, which is difficult to treat clinically. While it is well established that altered sensory processing in the spinal cord contributes to mechanical hypersensitivity (central sensitization), it is still debated whether primary afferent neurons become sensitized to mechanical stimuli after tissue inflammation. ⋯ Further, we pharmacologically anesthetized the TRPA1-expressing fibers in vivo by co-injecting the membrane-impermeable sodium channel inhibitor QX-314 and the TRPA1 agonist cinnamaldehyde into the hind paw. This approach also alleviated behavioral mechanical hyperalgesia in inflamed mice but left heat hypersensitivity intact. Our findings indicate that C-Mechano Cold sensitive fibers exhibit enhanced firing to suprathreshold mechanical stimuli in a TRPA1-dependent manner during inflammation, and that input from these fibers drives mechanical hyperalgesia in inflamed mice.
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Background and purpose A growing number of people are using computers. Shoulder and neck pain occur commonly during computer work. Peripheral and central sensitization may play a major role in establishing and maintaining several chronic pain conditions. ⋯ The development of pain during the computer work indicates peripheral sensitization as the predominant mechanism. Decreased pressure pain thresholds also in sites distant from pain areas may indicate a contribution from central sensitization in the subjects with chronic shoulder and neck pain. Implications The lasting pain after work and the reduced PPTs both in involved and distant musculature may indicate need for frequent pauses during computer work, especially when performed with time pressure and high precision demands, in order to avoid pain to increase and sustain after work, and thus to prevent the possibility of pain to become chronic.
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Hydrogen sulfide (H(2)S), which is produced endogenously from L-cysteine, is an irritant with pro-nociceptive actions. We have used measurements of intracellular calcium concentration, electrophysiology and behavioral measurements to show that the somatic pronociceptive actions of H(2)S require TRPA1. A H(2)S donor, NaHS, activated TRPA1 expressed in CHO cells and stimulated DRG neurons isolated from Trpa1(+/+) but not Trpa1(-/-) mice. ⋯ In behavioral studies, NaHS mediated sensitization was also inhibited by a T-type calcium channel inhibitor, mibefradil. In contrast to the effects of NaHS on somatic sensitivity, intracolonic NaHS administration evoked similar nociceptive effects in Trpa1(+/+) and Trpa1(-/-) mice, suggesting that the visceral pro-nociceptive effects of H(2)S are independent of TRPA1. In electrophysiological studies, the depolarizing actions of H(2)S on isolated DRG neurons were inhibited by AP-18, but not by mibefradil indicating that the primary excitatory effect of H(2)S on DRG neurons is TRPA1 mediated depolarization.