Novel therapies for cancer-induced bone pain.

Cancer pain is a growing problem, especially with the substantial increase in cancer survival. Reports indicate that bone metastasis, whose primary symptom is bone pain, occurs in 65-75% of patients with advanced breast or prostate cancer. We optimized a preclinical model of cancer-induced bone pain (CIBP) involving the injection of Lewis Lung Carcinoma cells into the intramedullary space of the femur of C57BL/6 mice or transgenic mice on a C57BL/6 background.

Analgesic targets identified in mouse sensory neuron somata and terminal pain translatomes.

The relationship between transcription and protein expression is complex. We identified polysome-associated RNA transcripts in the somata and central terminals of mouse sensory neurons in control, painful (plus nerve growth factor), and pain-free conditions (Nav1.7-null mice).

Virus-Induced MicroRNA Modulation and Systemic Sclerosis Disease.

MicroRNAs (miRNAs) are short noncoding RNA sequences that regulate gene expression at the post-transcriptional level. They are involved in the regulation of multiple pathways, related to both physiological and pathological conditions, including autoimmune diseases, such as Systemic Sclerosis (SSc). Specifically, SSc is recognized as a complex and multifactorial disease, characterized by vascular abnormalities, immune dysfunction, and progressive fibrosis, affecting skin and internal organs.

Chemogenetic Silencing of Na1.8-Positive Sensory Neurons Reverses Chronic Neuropathic and Bone Cancer Pain in FLEx PSAM-GlyR Mice.

Drive from peripheral neurons is essential in almost all pain states, but pharmacological silencing of these neurons to effect analgesia has proved problematic. Reversible gene therapy using long-lived chemogenetic approaches is an appealing option. We used the genetically activated chloride channel PSAM-GlyR to examine pain pathways in mice.

Gate control of sensory neurotransmission in peripheral ganglia by proprioceptive sensory neurons.

Melzak and Wall's gate control theory proposed that innocuous input into the dorsal horn of the spinal cord represses pain-inducing nociceptive input. Here we show that input from proprioceptive parvalbumin-expressing sensory neurons tonically represses nociceptor activation within dorsal root ganglia. Deletion of parvalbumin-positive sensory neurons leads to enhanced nociceptor activity measured with GCaMP3, increased input into wide dynamic range neurons of the spinal cord and increased acute and spontaneous pain behaviour, as well as potentiated innocuous sensation.