Pain
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Pain associated with bone cancer remains poorly managed, and chemotherapeutic drugs used to treat cancer usually increase pain. The discovery of dual-acting drugs that reduce cancer and produce analgesia is an optimal approach. The mechanisms underlying bone cancer pain involve interactions between cancer cells and nociceptive neurons. ⋯ Inhibition of ATX or blockade of LPAR attenuated cancer exosome-evoked hypersensitivity in an ATX-LPA-LPAR-dependent manner. Parallel in vitro studies revealed the involvement of ATX-LPA-LPAR signaling in direct sensitization of dorsal root ganglion neurons by cancer exosomes. Thus, our study identified a cancer exosome-mediated pathway, which may represent a therapeutic target for treating tumor growth and pain in patients with bone cancer.
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Migraine is commonly reported in patients with temporomandibular disorders (TMDs), but little is known about the mechanisms underlying the comorbid condition. Here, we prepared a mouse model to investigate this comorbidity, in which masseter muscle tendon ligation (MMTL) was performed to induce a myogenic TMD, and the pre-existing TMD enabled a subthreshold dose of nitroglycerin (NTG) to produce migraine-like pain in mice. ⋯ Moreover, chemogenetic activation of Pdyn -expressing neurons or microinjection of dynorphin A (1-17) peptide in the Sp5C enabled a subthreshold dose of NTG to induce migraine-like pain in female mice but not in male mice. Taken together, our results suggest that trigeminal dynorphin has a female-specific role in the modulation of comorbid TMDs and migraine.