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Query: UMLS:C0279530 (
bone cancer
)
1,036
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Primary and metastatic cancers that affect bone are frequently associated with severe and intractable pain. The mechanisms underlying the pathogenesis of
bone cancer
pain still remain largely unknown. Previously, we have reported that sensitization of primary sensory dorsal root ganglion (DRG) neurons contributes to the pathogenesis of
bone cancer
pain in rats. In addition, numerous preclinical and clinical studies have revealed the pathological roles of
interleukin-6
(
IL-6
) in inflammatory and neuropathic hyperalgesia. In this study, we investigated the role and the underlying mechanisms of
IL-6
in the development of
bone cancer
pain using in vitro and in vivo approaches. We first demonstrated that elevated
IL-6
in DRG neurons plays a vital role in the development of nociceptor sensitization and
bone cancer
-induced pain in a rat model through
IL-6
/soluble
IL-6
receptor (sIL-6R) trans-signaling. Moreover, we revealed that functional upregulation of transient receptor potential vanilloid channel type 1 (TRPV1) in DRG neurons through the activation of Janus kinase (JAK)/phosphatidylinositol 3-kinase (PI3K) signaling pathway contributes to the effects of
IL-6
on the pathogenesis of
bone cancer
pain. Therefore, suppression of functional upregulation of TRPV1 in DRG neurons by the inhibition of JAK/PI3K pathway, either before surgery or after surgery, reduces the hyperexcitability of DRG neurons and pain hyperalgesia in
bone cancer
rats. We here disclose a novel intracellular pathway, the
IL-6
/JAK/PI3K/TRPV1 signaling cascade, which may underlie the development of peripheral sensitization and
bone cancer
-induced pain.
...
PMID:Interleukin-6-mediated functional upregulation of TRPV1 receptors in dorsal root ganglion neurons through the activation of JAK/PI3K signaling pathway: roles in the development of bone cancer pain in a rat model. 2577 59
Interleukin-6
is an inflammatory cytokine with wide-ranging biological effects. It has been widely demonstrated that neuroinflammation plays a critical role in the development of pathological pain. Recently, various pathological pain models have shown elevated expression levels of
interleukin-6
and its receptor in the spinal cord and dorsal root ganglia. Additionally, the administration of
interleukin-6
could cause mechanical allodynia and thermal hyperalgesia, and an intrathecal injection of anti-
interleukin-6
neutralizing antibody alleviated these pain-related behaviors. These studies indicated a pivotal role of
interleukin-6
in pathological pain. In this review, we summarize the recent progress in understanding the roles and mechanisms of
interleukin-6
in mediating pathological pain associated with
bone cancer
, peripheral nerve injury, spinal cord injury, chemotherapy-induced peripheral neuropathy, complete Freund's adjuvant injection, and carrageenan injection. Understanding and regulating
interleukin-6
could be an interesting lead to novel therapeutic strategies for pathological pain.
...
PMID:Interleukin-6: an emerging regulator of pathological pain. 2726 59
