Pro-adrenomedullin (Pro-ADM) is a 185 amino acid long protein. It consists of a pro-ADM N-terminal 20 peptide (PAMP), a midregional pro-ADM (MR-proADM), an adrenotensin and a glycine-extended 53-amino acid peptides. The latter is subsequently converted to the mature ADM consisting of 52 amino acid by enzymatic amidation [].Adrenomedullin (ADM) is a hypotensive peptide, and was first discovered in human pheochromocytoma, it belongs to the calcitonin gene-related peptide family. The first described effects were vasodilation and blood pressure lowering effects but later, other actions were discovered in health and disease, among them stabilisation and development of the endothelial barrier and immunoregulation. ADM is widely expressed in virtually all human tissues with highest levels in adrenal medulla, cardiac atria, and lungs. Many cells are capable of producing ADM, including ECs, vascular smooth muscle cells (VSMCs), monocytes, renal parenchymal cells, and macrophages. ADM exerts its effects by interaction of its C-terminal moiety with ADM1 and ADM2 receptors which are complexes consisting of the calcitonin receptor-like receptor (CRLR) combined with a specific receptor activity-modifying protein 2 and 3 (RAMP2 and RAMP3), respectively, mostly referred to as "ADM receptors". These receptors have been detected in various tissues and organs, such as blood vessels, skeletal muscles, heart, lungs, and nerve tissue [].Recently, ADM has been characterised as pronociceptive mediator, acting as an upstream factor in the transmission of noxious information for various types of pathological pain including acute and chronic inflammatory pain, cancer pain, neuropathic pain induced by spinal nerve injury and diabetic neuropathy. It may also have a role in nerve regeneration in pathological conditions [].
