<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Spinal cord circuits underlying dynamic and punctate allodynia in inflammatory pain & Cellular basis for prefrontal modulation of inflammatory pain by fear"^^ . "One of the characteristics of inflammatory pain is mechanical allodynia, which occurs in distinct forms, including dynamic and punctate mechanical allodynia. Although the spinal cord circuitry of mechanical allodynia is well understood in terms of postsynaptic inhibition, the contribution of presynaptic inhibition to these distinct forms is not clear. Here, we used an IEG-based dual epoch method to simultaneously visualize the population correlates and the circuitry involved in these two contrasting types of mechanical allodynia in the spinal cord dorsal horn at a single-cell resolution. To investigate the role of presynaptic inhibition in these circuits, we also generated mice conditionally lacking GABAA receptors in DRG sensory neurons (Advillin-GABAAβ3-/-) or nociceptive neurons (SNS-GABAAβ3-/-). In conditions of inflammatory pain induced by paw inflammation, SNS-GABAAβ3-/- mice did not develop punctate mechanical allodynia, while dynamic mechanical allodynia was still preserved. We observed that punctate and dynamic mechanical stimuli shape distinct activation patterns of intermingled neurons in the spinal cord dorsal horn under inflammatory pain conditions. Only the neuronal population activated by punctate mechanical stimuli was significantly reduced in SNS-GABAAβ3-/- mice as compared to control littermates. The activation of spinal neurons expressing Calretinin and Parvalbumin activated by punctate mechanical stimuli was significantly reduced in SNS-GABAAβ3-/- mice. Collectively with previous studies, these results support the hypothesis that presynaptic GABAergic inhibition switches to excitation in nociceptors under inflammatory pain conditions, and particularly modulates punctate mechanical allodynia. Moreover, this study is amongst the first to visualize the circuit population of these two distinct forms of mechanical allodynia and demonstrates the distinct, but intermingled, patterns shared between them. This work has significant impact on the current consideration of GABA-modulating drugs as analgesics and suggests that the switch from inhibition to excitation may be a hindrance.\r\n\r\nFear has a significant impact on one's subjective perception of pain and is involved in the development of chronic pain. However, mechanistic understanding and causal investigation of the underlying cellular substrates are lacking. Formerly, we observed silencing the remote fear retrieval engram specifically inhibited subsequent tonic pain without eliciting a generalized impairment of associative learning or aversion. Here, to further address whether directly activating prefrontal fear memory engrams after fear conditioning can facilitate tonic pain perception, we employed activity-based cell-tagging and optogenetic approaches to activates the neuronal assemblies for remote fear recall. Furthermore, to investigate whether established chronic inflammatory pain perception can be reduced by inhibition of these prefrontal cellular substrates of fear memory, we performed similar approaches to identify and inhibit the neuronal assemblies for remote fear recall in the mouse prefrontal cortex under chronic inflammatory pain conditions. We report that cell assemblies representing long-term fear retrieval and inflammatory heat pain are largely distinct, but a smaller overlapping subset also exists in the prefrontal cortex. Activation of the remote fear retrieval engram specifically promoted subsequent tonic pain perception and pain-related behavior. Under inflammatory pain conditions, suppression of remote fear engram reduced inflammatory heat hypersensitivity, without causing an associative avoidance or aversion deficiency. These findings provide a further understanding about how long-term fear prospectively shapes the experience of tonic pain and inflammatory pain. Moreover, our data reveal the fundamental cellular mechanism in the prefrontal cortex causally mediating this synergistic interaction, thereby laying a basis for future interventional therapies in patients with chronic pain and fear."^^ . "2022" . . . . . . . "Sheng"^^ . "Liu"^^ . "Sheng Liu"^^ . . . . . . "Spinal cord circuits underlying dynamic and punctate allodynia in inflammatory pain & Cellular basis for prefrontal modulation of inflammatory pain by fear (PDF)"^^ . . . "Thesis of Sheng Liu V4 for print.pdf"^^ . . . "Spinal cord circuits underlying dynamic and punctate allodynia in inflammatory pain & Cellular basis for prefrontal modulation of inflammatory pain by fear (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Spinal cord circuits underlying dynamic and punctate allodynia in inflammatory pain & Cellular basis for prefrontal modulation of inflammatory pain by fear (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Spinal cord circuits underlying dynamic and punctate allodynia in inflammatory pain & Cellular basis for prefrontal modulation of inflammatory pain by fear (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Spinal cord circuits underlying dynamic and punctate allodynia in inflammatory pain & Cellular basis for prefrontal modulation of inflammatory pain by fear (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Spinal cord circuits underlying dynamic and punctate allodynia in inflammatory pain & Cellular basis for prefrontal modulation of inflammatory pain by fear (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #31329 \n\nSpinal cord circuits underlying dynamic and punctate allodynia in inflammatory pain & Cellular basis for prefrontal modulation of inflammatory pain by fear\n\n" . "text/html" . . . "610 Medizin"@de . "610 Medical sciences Medicine"@en . .