The Proteomics of Intrathecal Analgesic agents for Chronic Pain

Abstract

Chronic pain remains a challenging clinical problem with a growing socio-economic burden for the state. Its prevalence is high and many of the patients are of work age. Our knowledge regarding the pathophysiology of chronic pain is poor. The consensus view is that the central nervous system plays a key role in the persistence of pain after an initiating event has long ceased. However the specifics of this biological response to an initiating event remains unclear. There is a growing body of evidence to support the concept that a central neuroimmune response is initiated and a number of small peptides have been implicated in this process following cerebrospinal fluid analysis in patients with chronic pain. This central biosynthetic peptide response leads to a process called central sensitization. Therapy is aimed at modulating and even inhibiting this response. However current pharmacological therapeutic options are limited in efficacy with significant deleterious side effect profiles. Proteomic studies extend single molecule analysis by identifying the components of biological networks and pathways and defining their interactions. This tool offers the potential to provide a molecular overview of the biological processes involved in chronic pain. It will also facilitate examination of gene-drug interactions. This technique offers a mechanism of defining the central biological responses that result in chronic pain and this information may facilitate the development of better therapies.

Computational Functional Genomics-Based Approaches in Analgesic Drug Discovery and Repurposing

“…By extending single molecule analyses to whole biological networks and pathways, a molecular overview of the biological processes involved in chronic pain can be obtained [112]. Indeed, an analysis of spinal protein expression in rats exposed to repeated intrathecal injection of morphine to investigate morphine tolerance and addiction identified eight regulated proteins possibly qualifying as targets for the prevention of morphine tolerance [113].…”

EDITORIAL (Thematic Selection: Spinal Neuropharmacological Agents for the Management of Pain)

“…Moore and McCrory present the first review investigating proteomic changes associated with intrathecal morphine, hydromorphone, fentanyl, bupivicaine, methyprednisolone, baclofen, clonidine, and ziconotide [ 15 ]. This review discusses common proteomic pathways associated with the initiation and maintenance of neuropathic pain, and the mechanism of action of intrathecal analgesics.…”

Epigenetic and Proteomic Signatures for Chronic Pain Patients after Total Knee Replacement

“…Interesting insights into modifications related to painful pathologies in preclinical and clinical studies have been described by research that aimed to evaluate the biological systems behind the complex molecular pathways that contribute to chronic pain, such as next-generation sequencing genomics 2,291 and epigenomic and transcriptomic studies 127,235 . Preclinical proteomic studies have focused on different aspects such as mice and rat models, which includes spinal nerve injury (SNI), spinal cord injury (SCI), Complete Freud's Adjuvant (CFA), and spinal nerve ligation (SNL) 142,146,224,244 , and investigated changes in proteins levels in response to drug administration 189 , highlighting several proteins dysregulation involved in response mechanism after painful and stress stimuli and inflammatory pathways 142,180 . In humans, only a few studies have focused on the proteomics approach to asses pain mechanisms and highlight potential biomarkers in tissue biopsies in order to study painful conditions like chronic widespread pain 202,203 , Complex Regional Pain Syndrome 198 , and myalgia 97,201 .…”