Overexpression of suppressor of cytokine signaling 3 in dorsal root ganglion attenuates cancer-induced pain in rats

Abstract

BackgroundCancer-induced pain (CIP) is one of the most severe types of chronic pain with which clinical treatment remains challenging and the involved mechanisms are largely unknown. Suppressor of cytokine signaling 3 (SOCS3) is an important intracellular protein and provides a classical negative feedback loop, thus involving in a wide variety of processes including inflammation and nociception. However, the role of SOCS3 pathway in CIP is poorly understood. The present study was designed to investigate the role of SOCS3 in dorsal root ganglion (DRG) in the development of CIP.MethodCIP was established by injection of Walker 256 mammary gland tumor cells into the rat tibia canal. Whole-cell patch clamping and Western blotting were performed.ResultsFollowing the development of bone cancer, SOCS3 expression was significantly downregulated in rat DRGs at L2–L5 segments. Overexpression of SOCS3, using lentiviral-mediated production of SOCS3 at spinal cord level, drastically attenuated mechanical allodynia and body weight-bearing difference, but not thermal hyperalgesia in bone cancer rats. In addition, overexpression of SOCS3 reversed the hyperexcitability of DRG neurons innervating the tibia, and reduced abnormal expression of toll-like receptors 4 in the DRGs.ConclusionsThese results suggest that SOCS3 might be a key molecular involved in the development of complicated cancer pain and that overexpression of SOCS3 might be an important strategy for treatment for mechanical allodynia associated with bone cancer.

Prenatal maternal stress induces visceral hypersensitivity of adult rat offspring through activation of cystathionine-β-synthase signaling in primary sensory neurons

“…Gestational psychosocial factors lead to increased inflammation, which influences the development of adult gastrointestinal disease. Maternal psychosocial factors contribute to higher circulating levels of inflammation markers, such as H 2 S 33 and the proinflammatory cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and TRL4, 34 which are involved in many pain condition, such as bone cancer pain 35 , 36 and neuropathic pain. 37 As reviewed by Entringer et al., H 2 S had a direct programming effects of maternal inflammation.…”

Transcriptomic sex differences in sensory neuronal populations of mice

“…4E) 34,35 . It is also possible that higher expression of these DEGs in female sensory neurons could play a protective role during pain conditions [35][36][37] .…”

Upregulation of Spinal Voltage-Dependent Anion Channel 1 Contributes to Bone Cancer Pain Hypersensitivity in Rats

“…Mechanical allodynia was assessed using the up-down method in the hind paw withdrawal response to von Frey fillament (VFF) stimulation. The 50% paw withdrawal threshold (PWT) was determined as previously described [19,21,22]. Each rat was placed in a transparent box and allowed to acclimate to the surroundings for at least 30 min.…”

“…The cutoff force was set at 15.0 g. Each stimulation was spaced at *10-min intervals and the mean value was regarded as the strength to produce a withdrawal response. The paw withdrawal latency (PWL) to thermal hyperalgesia was measured as previously reported [19,21]. Rats were placed on a clear glass plate and allowed to acclimate to the new surroundings for 30 min.…”

“…Our previous studies have shown that rats treated with Walker 256 tumor cells display a gradual increase in sensitivity to VFF and radiant heat stimuli 2 weeks after tumor cell injection [19,21]. Therefore, we began our current studies at week 2 after tumor cell injection.…”