Cancer pain is not necessarily correlated with spinal overexpression of reactive glia markers

Abstract

Bone cancer pain is a common and disruptive symptom in cancer patients. In cancer pain animal models, massive reactive astrogliosis in the dorsal horn of the spinal cord has been reported. Because astrocytes may behave as driving partners for pathological pain, we investigated the temporal development of pain behavior and reactive astrogliosis in a rat bone cancer pain model induced by injecting MRMT-1 rat mammary gland carcinoma cells into the tibia. Along with the development of bone lesions, a gradual mechanical and thermal allodynia and hyperalgesia as well as a reduced use of the affected limb developed in bone cancer-bearing animals, but not in sham-treated animals. Dorsal horn Fos expression after nonpainful palpation of the injected limb was also increased in bone cancer-bearing animals. However, at any time during the evolution of tumor, there was no increase in glial fibrillary acidic protein (GFAP) immunoreactivity in the dorsal horn. Further analysis at 21days after injection of the tumor showed no increase in GFAP and interleukin (IL) 1β transcripts, number of superficial dorsal horn S100β protein immunoreactive astrocytes, or immunoreactivity for microglial markers (OX-42 and Iba-1). In contrast, all these parameters were increased in the dorsal horn of rats 2weeks after sciatic nerve ligation. This suggests that in some cases, bone cancer pain may not be correlated with spinal overexpression of reactive glia markers, whereas neuropathic pain is. Glia may thus play different roles in the development and maintenance of chronic pain in these 2 situations.

TACAN is an essential component of the mechanosensitive ion channel responsible for pain sensing

“…Given that the withdrawal response can be the result of spinal reflexes, we also examined the mouse behavior for evidence of pain-related responses, such as paw flicking or licking, as previously described (Ducourneau et al, 2014). When the intensity of the mechanical stimulus rose above the withdrawal threshold, mice began to display nociceptive-like behaviors ( Figure 6B).…”

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

“…with sham rats, which indicates that astrogliosis and synaptic plasticity had developed. Interestingly, a recent study reported that both microglia and astrocytes were unnecessary for BCP [43] . We speculate that this discrepancy may be a result of differences in the inoculated carcinoma cell lines and experimental animal species; however, further study is required to clarify this intriguing issue.…”

Pattern recognition receptors in chronic pain: Mechanisms and therapeutic implications

“…HIV-associated neuropathic pain (Shi et al, 2012) and metastatic tumour-induced bone cancer (Ducourneau et al, 2014). Therefore, although the releasing mechanisms in response to a peripheral injury remains uncertain, centrally released DAMP molecules can serve as messenger molecules that convey the information of peripheral tissue/nerve damage to the CNS through the activation of PRRs expressed in the CNS cells, thereby contributing to the central sensitization.…”

“…Moreover, the activation of the S100β/RAGE pathway in microglia has also been associated with the upregulation of COX-2 via the JNK and NF-kB intracellular signalling pathways . Because an increased expression of S100β in the spinal cord has been shown in various chronic pain models, such as spinal nerve ligation (Tanga et al, 2006), CFA-induced paw inflammation and bone cancer pain (Ducourneau et al, 2014), it is possible that S100β/microglial RAGE signalling may contribute to central sensitization.…”