Biomarkers for Better Understanding of the Pathophysiology and Treatment of Chronic Pain [Elektronisk resurs] Investigations of Human Biofluids

• Chronic pain affects 20 % of the global population, causes suffering, is difficult to treat, and constitutes a large economic burden for society. So far, the characterization of molecular mechanisms of chronic pain-like behaviors in animal models has not translated into effective treatments. In this thesis, consisting of five studies, pain patient biofluids were analyzed with modern proteomic methods to identify biomarker candidates that can be used to improve our understanding of the pathophysiology chronic pain and lead to more effective treatments. Paper I is a proof of concept study, where a multiplex solid phase-proximity ligation assay (SP-PLA) was applied to cerebrospinal fluid (CSF) for the first time. CSF reference protein levels and four biomarker candidates for ALS were presented. The investigated proteins were not altered by spinal cord stimulation (SCS) treatment for neuropathic pain. In Paper II, patient CSF was explored by dimethyl and label-free mass spectrometric (MS) proteomic methods. Twelve proteins, known for their roles in neuroprotection, nociceptive signaling, immune regulation, and synaptic plasticity, were identified to be associated with SCS treatment of neuropathic pain. In Paper III, proximity extension assay (PEA) was used to analyze levels of 92 proteins in serum from patients one year after painful disc herniation. Patients with residual pain had significantly higher serum levels of 41 inflammatory proteins. In Paper IV, levels of 55 proteins were analyzed by a 100-plex antibody suspension bead array (ASBA) in CSF samples from two neuropathic pain patient cohorts, one cohort of fibromyalgia patients and two control cohorts. CSF protein profiles consisting of levels of apolipoprotein C1, ectonucleotide pyrophosphatase/phosphodiesterase family member 2, angiotensinogen, prostaglandin-H2 D-isomerase, neurexin-1, superoxide dismutases 1 and 3 were found to be associated with neuropathic pain and fibromyalgia. In Paper V, higher CSF levels of five chemokines and LAPTGF-beta-1were detected in two patient cohorts with neuropathic pain compared with healthy controls. In conclusion, we demonstrate that combining MS proteomic and multiplex antibody-based methods for analysis of patient biofluid samples is a viable approach for discovery of biomarker candidates for the pathophysiology and treatment of chronic pain. Several biomarker candidates possibly reflecting systemic inflammation, lipid metabolism, and neuroinflammation in different pain conditions were identified for further investigation. 

Ämnesord

Medical and Health Sciences  (hsv)

Clinical Medicine  (hsv)

Anesthesiology and Intensive Care  (hsv)

Medicin och hälsovetenskap  (hsv)

Klinisk medicin  (hsv)

Anestesi och intensivvård  (hsv)

Clinical Laboratory Medicine  (hsv)

Klinisk laboratoriemedicin  (hsv)

Medical Biotechnology  (hsv)

Biomedical Laboratory Science/Technology  (hsv)

Medicinsk bioteknologi  (hsv)

Biomedicinsk laboratorievetenskap/teknologi  (hsv)

Natural Sciences  (hsv)

Chemical Sciences  (hsv)

Analytical Chemistry  (hsv)

Naturvetenskap  (hsv)

Kemi  (hsv)

Analytisk kemi  (hsv)

Anestesiologi och intensivvård  (uu)

Anaesthesiology and Intensive Care  (uu)

Biomedical Laboratory Science  (uu)

Biomedicinsk laboratorievetenskap  (uu)

Kemi med inriktning mot analytisk kemi  (uu)

Chemistry with specialization in Analytical Chemistry  (uu)

Medicinsk vetenskap  (uu)

Medical Science  (uu)

Molekylär medicin  (uu)

Molecular Medicine  (uu)

Indexterm och SAB-rubrik

chronic pain

neuropathic pain

lumbar radicular pain

amyotrophic lateral sclerosis

radiculopathy

fibromyalgia

pathophysiology

spinal cord stimulation

mechanism of action

disc herniation

cerebrospinal fluid

plasma

biomarker

human

protein

chemokines

cytokines

inflammation

neuroinflammation

mass spectrometry

proximity ligation assay

proximity extension assay

antibody suspension bead array

protein profiling

molecular medicine

personalized medicine