Development of selective sigma-1 receptor ligands with antiallodynic activity: A focus on piperidine and piperazine scaffolds.

The design and synthesis of a series of piperidine and piperazine-based derivatives as selective sigma receptor (SR) ligands associated with analgesic activity, are the focus of this work. In this study, affinities at S1R and S2R were measured, and molecular modeling studies were performed to investigate the binding pose features. The most promising compounds were subjected to in vitro toxicity testing and subsequently screened for in vivo analgesic properties.

The role of neutrophils in pain: systematic review and meta-analysis of animal studies.

The peripheral inflammatory response is an attractive therapeutic target for pain treatment. Neutrophils are the first circulating inflammatory cells recruited to sites of injury, but their contribution to pain outcomes is unclear. We performed a systematic review and meta-analysis of original preclinical studies, which evaluated the effect of preemptive neutrophil depletion on pain outcomes (PROSPERO registration number: CRD42022364004).

Pharmacological differences in postoperative cutaneous sensitivity, pain at rest, and movement-induced pain in laparotomized mice.

Postoperative pain management is challenging. We used mice with a transverse laparotomy to study tactile allodynia measured by the von Frey test, pain at rest measured by facial pain expressions detected by an artificial intelligence algorithm, and movement-induced pain measured by reductions in exploratory activity. The standard analgesics morphine and ibuprofen induced distinct patterns of outcome-dependent effects.

Sigma-1 Receptors Control Neuropathic Pain and Peripheral Neuroinflammation After Nerve Injury in Female Mice: A Transcriptomic Study.

The mechanisms for neuropathic pain amelioration by sigma-1 receptor inhibition are not fully understood. We studied genome-wide transcriptomic changes (RNAseq) in the dorsal root ganglia (DRG) from wild-type and sigma-1 receptor knockout mice prior to and following Spared Nerve Injury (SNI). In wildtype mice, most of the transcriptomic changes following SNI are related to the immune function or neurotransmission.

Nociceptor-immune interactomes reveal insult-specific immune signatures of pain.

Inflammatory pain results from the heightened sensitivity and reduced threshold of nociceptor sensory neurons due to exposure to inflammatory mediators. However, the cellular and transcriptional diversity of immune cell and sensory neuron types makes it challenging to decipher the immune mechanisms underlying pain. Here we used single-cell transcriptomics to determine the immune gene signatures associated with pain development in three skin inflammatory pain models in mice: zymosan injection, skin incision and ultraviolet burn.