The article by Wu et al. provided for a highly interesting reading (Wu et al., 2012). Interestingly, the past few months has seen the identification of a number of other new pathways that may be involved in the development of bone cancer pain.
For instance, recent data suggest that activation of the Jun N-terminal kinase (JNK) pathway in the spinal cord is necessary for the initiation of bone cancer pain. In fact, peripheral mechanical allodynia is markedly attenuated following intrathecal injection of JNK inhibitors such as SP600125 (Wang et al., 2012). Similarly, CX3CR1 has recently been shown to play a role in bone cancer pain by virtue of activating the p38 mitogen-activated protein kinase (MAPK) pathway (Hu et al. 2012a). Mechanical allodynia is markedly attenuated following intrathecal administration of anti-CX3CR1 antibodies by virtue of the down-regulation of p38 MAPK.
Recent data also suggest that the chemokine monocyte chemoattractant protein-1 (MCP-1) is involved in the aetiology of bone cancer pain. For instance, increased expression of spinal cord MCP-1 and its receptor CCR-2 is seen during the evolution of bone cancer pain in animal models (Hu et al. 2012b). Recent studies also suggest that activation of the protein kinase A (PKA) signalling pathway via activation of spinal TDAG8 also contributes significantly to the development of bone cancer pain (Hang et al., 2012). Not surprisingly, the intrathecal injection of the PKA inhibitor, H-89 markedly decreases the pain response to nociceptive stimuli.
The examples shown earlier clearly indicate that a number of different pathways are involved in the development of bone cancer pain. Further research is needed to further identify any other pathways and potential antagonists that may play a major role in the pain management of bone cancer pain.