In a new investigation scientists have discovered the pain relief effects of a vasodilator peptide hormone named Adrenomedullin, against bone cancer pain in a rat model1.
Pain induced by Bone cancer is common, hypersensitive and spontaneous one2. It is the most severe kind of pain which reduces the quality of life with increased morbidity ratio3. Several clinical medicines like; opiates, are considered effective for bone cancer pain but with adverse side effects4.
Underlying pain mechanism is not so clear. It is thought that up-regulation of pronociceptive (not leading to pain) mediators in dorsal root ganglia or the spinal cord has a role in bone cancer pain. Some of the pronociceptive mediators that are involved in bone cancer pain pathogenesis includes; sodium channels, CCL2 gene, CGRP (calcitonin gene-related peptide), nNOS (neuronal nitric oxide synthesis), interleukin-1β and PAR2 (protease-activated receptor 2)5-7.
Adrenomedullin (AM) is an important pain mediator. It may be involved in bone cancer pain. It is amino acid peptide and a member of calcitonin gene related peptide (CGRP) family. This peptide is expressed in superficial laminae of the spinal cord and small as well as medium diameter neurons in dorsal root ganglia (DRG) which is the key structures involved in nociceptive (pain) processing. It recruits the CGRP, nNOS and inflammatory cytokines8.
All the above factors lead the scientists to perform the study in order to investigate the possible role and involvement of Adrenomedullin in bone cancer pain. Experiment was designed by injection of carcinoma cells in medullar cavity of tibia in rats. Agents were intrathecally included in spinal cord. Nociceptive behaviors were assessed. Neuro-chemicals in the spinal dorsal horn and dorsal root ganglia (DRG) were assayed by immune-histo-chemistry and real-time PCR.
Authors explained the study outcome as;
“The increase in the activity of pronociceptive mediators is one of mechanisms underlying bone cancer pain. Our study extends this notion by adding AM, a recently characterized pronociceptive mediator, to the list of molecules involved in the pathogenesis of cancer pain. The key contribution of AM to bone cancer pain was evidenced not only by its up-regulation in the spinal dorsal horn and DRG but also by the inhibition of pain and cancer induced increase in AM, CGRP and nNOS following the blockade of AM receptors. These findings suggest that inhibition of AM receptor signaling might be a valuable therapy for bone cancer pain”
Written by: Rabeeia
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17 November, 2019