Pain
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Toll-like receptors (TLRs) play a pivotal role in inflammatory processes, and individual TLRs have been investigated in nociception. We examined overlapping and diverging roles of spinal TLRs and their associated adaptor proteins in nociceptive processing. Intrathecal (IT) TLR2, TLR3, or TLR4 ligands (-L) evoked persistent (7-day) tactile allodynia (TA) that was abolished in respective TLR-deficient mice. ⋯ Hence, spinal TIR domain-containing adaptor protein (TIRAP) and TRIF cascades differentially lead to robust TA by TNF-dependent and independent pathways, whereas activation of TRIF modulated processing through type I IFN receptors. Based on these results, we believe that processes leading to the activation of these spinal TLRs initiate TNF-dependent and -independent cascades, which contribute to the associated persistent pain state. In addition, TRIF pathways are able to modulate the TNF-dependent pain state through IFNβ.
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Given the inherent variability in pain responding, using an "average" pain score may pose serious threats to internal and external validity. Using growth mixture modeling (GMM), this article first examines whether infants can be differentiated into stable groups based on their pain response patterns over a 2-minute post-needle period. Secondary analyses, to specifically address the issue of averaging pain scores to represent a sample, qualitatively described clinically meaningful differences between pain scores of the discerned groups and the overall mean (irrespective of groups). ⋯ Our secondary suggested that the overall mean pain score immediately post-needle reflected most groups well at every age. However, for older infants (6 and 12months, especially), the overall mean pain responses at 1 and 2minutes post-needle significantly over or underestimated groups that contained 48% to 100% of the sample. These results combined highlight the significant variability of infant pain responding patterns between groups of infants and furthermore, calls into question the validity of using an overall mean in research with older infants during the regulatory phase post-needle.
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Review Meta Analysis
Prevalence and natural history of pain in adults with multiple sclerosis: systematic review and meta-analysis.
The prevalence, associations, and natural history of pain in multiple sclerosis (MS) are poorly understood. The objective of this work was to study the prevalence of pain syndromes in MS both cross-sectionally, and longitudinally during the MS disease course. We systematically identified prospective studies detailing pain prevalence in definite MS. ⋯ Pain is common in MS, as are specific pain syndromes. The clinical associations and natural history of pain in MS require clarification. Future study could be enhanced by standardised study design.