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Item CaMKII Controls Whether Touch Is Painful(Society for Neuroscience, 2015-10-21) Yu, Hongwei; Pan, Bin; Weyer, Andy; Wu, Hsiang-En; Meng, Jingwei; Fischer, Gregory; Vilceanu, Daniel; Light, Alan R.; Stucky, Cheryl; Rice, Frank L.; Hudmon, Andy; Hogan, Quinn; Department of Biochemistry & Molecular Biology, IU School of MedicineThe sensation of touch is initiated when fast conducting low-threshold mechanoreceptors (Aβ-LTMRs) generate impulses at their terminals in the skin. Plasticity in this system is evident in the process of adaption, in which a period of diminished sensitivity follows prior stimulation. CaMKII is an ideal candidate for mediating activity-dependent plasticity in touch because it shifts into an enhanced activation state after neuronal depolarizations and can thereby reflect past firing history. Here we show that sensory neuron CaMKII autophosphorylation encodes the level of Aβ-LTMR activity in rat models of sensory deprivation (whisker clipping, tail suspension, casting). Blockade of CaMKII signaling limits normal adaptation of action potential generation in Aβ-LTMRs in excised skin. CaMKII activity is also required for natural filtering of impulse trains as they travel through the sensory neuron T-junction in the DRG. Blockade of CaMKII selectively in presynaptic Aβ-LTMRs removes dorsal horn inhibition that otherwise prevents Aβ-LTMR input from activating nociceptive lamina I neurons. Together, these consequences of reduced CaMKII function in Aβ-LTMRs cause low-intensity mechanical stimulation to produce pain behavior. We conclude that, without normal sensory activity to maintain adequate levels of CaMKII function, the touch pathway shifts into a pain system. In the clinical setting, sensory disuse may be a critical factor that enhances and prolongs chronic pain initiated by other conditions. SIGNIFICANCE STATEMENT: The sensation of touch is served by specialized sensory neurons termed low-threshold mechanoreceptors (LTMRs). We examined the role of CaMKII in regulating the function of these neurons. Loss of CaMKII function, such as occurred in rats during sensory deprivation, elevated the generation and propagation of impulses by LTMRs, and altered the spinal cord circuitry in such a way that low-threshold mechanical stimuli produced pain behavior. Because limbs are protected from use during a painful condition, this sensitization of LTMRs may perpetuate pain and prevent functional rehabilitation.Item Women's techniques for pleasure from anal touch: Results from a U.S. probability sample of women ages 18-93(PLOS, 2022-06-29) Hensel, Devon J.; von Hippel, Christiana D.; Lapage, Charles C.; Perkins, Robert H.; Pediatrics, School of MedicineThe study purpose was to assess, in a U.S. probability sample of women, the specific ways women have discovered to experience pleasure from anal touch. Through qualitative pilot research with women that informed the development of the survey instrument used in this study, we identified three previously unnamed, but distinct, anal touch techniques that many women find pleasurable and that expand the anal sexual repertoire beyond the more commonly studied anal intercourse behaviors: Anal Surfacing, Anal Shallowing, and Anal Pairing. This study defines each technique and describes its prevalence among U.S. adult women. Weighted frequencies were drawn from the Second OMGYES Pleasure Report-a cross-sectional, online, national probability survey of 3017 American women's (age 18-93) sexual experiences and discoveries. Participants were recruited via the Ipsos KnowledgePanel®. Data suggest that 40% of women find 'Anal Surfacing' pleasurable: sexual touch by a finger, penis, or sex toy on and around the anus. Approximately 35% of women have experienced pleasure using 'Anal Shallowing': penetrative touch by a finger, penis, or sex toy just inside the anal opening, no deeper than a fingertip/knuckle. Finally, 40% of women make other forms of sexual touch more pleasurable using 'Anal Pairing': touch on or inside the anus that happens at the same time as other kinds of sexual touch such as vaginal penetration or clitoral touching. These data provide techniques that women can and do use to explore the anus as a pleasurable region for touch-which can enable women to better identify their own preferences, communicate about them and advocate for their sexual pleasure.