Pain
-
Head and neck squamous cell carcinoma (HNSCC) causes more severe pain and psychological stress than other types of cancer. Despite clinical evidence linking pain, stress, and cancer progression, the underlying relationship between pain and sympathetic neurotransmission in oral cancer is unknown. We found that human HNSCC tumors and mouse tumor tissue are innervated by peripheral sympathetic and sensory nerves. ⋯ Furthermore, chemical sympathectomy using guanethidine led to a significant reduction in tumor size and nociceptive behavior. We infer from these results that sympathetic signaling modulates oral cancer pain through TNFα secretion and tumorigenesis. Further investigation of the role of neurocancer communication in cancer progression and pain is warranted.
-
Nerve trauma-induced alternations of gene expression in the neurons of dorsal root ganglion (DRG) participate in nerve trauma-caused nociceptive hypersensitivity. Transcription factors regulate gene expression. Whether the transcription factor E74-like factor 1 (ELF1) in the DRG contributes to neuropathic pain is unknown. ⋯ Mechanistically, more ELF1 directly bond to and activated Mmp9 promoter in injured DRG neurons after CCI. Our data indicate that ELF1 participates in nerve trauma-caused nociceptive hypersensitivity likely through upregulating MMP9 in injured DRG. E74-like factor 1 may be a new target for management of neuropathic pain.
-
Ambroxol is a multifaceted drug with primarily mucoactive and secretolytic actions, along with anti-inflammatory, antioxidant, and local anaesthetic properties. It has a long history of use in the treatment of respiratory tract diseases and has shown to be efficacious in relieving sore throat. In more recent years, ambroxol has gained interest for its potential usefulness in treating neuropathic pain. ⋯ With its well-established safety profile, extensive preclinical and clinical drug data, and early evidence of clinical effectiveness, ambroxol is an old drug worthy of further investigation for repurposing. As a patent-expired drug, a push is needed to progress the drug to clinical trials for neuropathic pain. We encourage the pharmaceutical industry to look at patented drug formulations and take an active role in bringing an optimized version for neuropathic pain to market.
-
An ACVR1 activating mutation causes neuropathic pain and sensory neuron hyperexcitability in humans.
Altered bone morphogenetic protein (BMP) signaling is associated with many musculoskeletal diseases. However, it remains unknown whether BMP dysfunction has direct contribution to debilitating pain reported in many of these disorders. Here, we identified a novel neuropathic pain phenotype in patients with fibrodysplasia ossificans progressiva (FOP), a rare autosomal-dominant musculoskeletal disorder characterized by progressive heterotopic ossification. ⋯ Although there was no major effect of ACVR1 R206H on differentiation and maturation of nociceptive sensory neurons (iSNs) derived from FOP induced pluripotent stem cells, both intracellular and extracellular electrophysiology analyses of the ACVR1 R206H iSNs displayed ACVR1-dependent hyperexcitability, a hallmark of neuropathic pain. Consistent with this phenotype, we recorded enhanced responses of ACVR1 R206H iSNs to TRPV1 and TRPA1 agonists. Thus, activated ACVR1 signaling can modulate pain processing in humans and may represent a potential target for pain management in FOP and related BMP pathway diseases.
-
Evaluation of opioid switching (OS) for cancer pain has not been properly assessed. The aim of this study was to assess an integrated score (Maddalena Opioid Switching Score) as a simple and repeatable tool to evaluate the outcomes of OS, facilitating the interpretation and comparison of studies, and information exchange among researchers. The integrated score took into account pain intensity, intensity of opioid-related symptoms, and cognitive function by using an author's formula. ⋯ In patients with unsuccessful OS, no significant changes in the Maddalena Opioid Switching Score and PGI were observed. A significant reduction in Edmonton Symptom Assessment Scale items intensity was observed after OS. The Maddalena Opioid Switching Score resulted to be a sensitive instrument for measuring the clinical improvement produced by OS.