Neurobiological Basis of Pain Syndrome in War Veterans with PTSD: Preliminary Findings
Authors: Pivac Nela  , Nedic Gordana  , Nikolac Matea  , Fistonic Marina  , Kovacevic Marin  , Mustapic Maja  , Gveric Korkut Ines  , Grubisic-Ilic Mirjana  , Kozaric-Kovacic Dragica  , Muck-Seler Dorotea  
Published: February 2025

Posttraumatic Stress Disorder (PTSD) is assumed to represent a marker of stress vulnerability rather than a reaction after exposure to a trauma. The underlying biology of PTSD consists of the pre-traumatic biological and physiological risk factors that affect the ability to cope with the traumatic event. Diagnoses involving pain are extremely common among war veterans. The prevalence of chronic pain occurs more frequently in subjects with PTSD (25-80%) than in control subjects, while chronic pain patients have more frequent PTSD than other groups. It is proposed that PTSD mediates chronic pain symptoms. The biological substrates of vulnerability to PTSD and pain include central neurotransmitters, neurotrophic factors, and neuroendocrine systems, while physiological factors include those related to attention, hyperarousal, avoidance, cognition, and anxiety. The severity of PTSD has been found to be correlated with the severity of chronic pain. The neurobiological mechanisms underlying altered pain perception in combat exposed veterans with PTSD are still unclear. Therefore, the aim of this preliminary study was to assess peripheral biomarkers (platelet serotonin [5-HT] concentration, platelet monoamine oxidase type B [MAO-B] activity) and to determine genetic polymorphisms of MAO-B, dopamine-beta-hydroxylase (DBH), catechol-o-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF), serotonin transporter (5-HTT), and serotonin 5HT2A receptor, in male Croatian war veterans with current and chronic combat-related PTSD subdivided into those with or without pain syndrome. The objectives were to elucidate the distribution of the genotypes or alleles for MAO-B intron 13, - 1021C/T DBH, Val158/108Met COMT, Val66Met BDNF, 102T/C 5HT2A polymorphisms and 5-HTT gene-linked polymorphic region (5-HTTLPR), and to explore the relation between these variants and pain syndrome in combat-related PTSD. The hypothesis of this study was that these biomarkers would differ between veterans with or without pain syndrome. Since it has been shown that early treatment of pain would prevent the development of chronic pain syndrome, this study aimed to find biomarkers that would provide earlier treatment of pain syndrome, in order to reduce consequences of the pain-related conditions in veterans with PTSD. Participants (N=142) included in the study were unrelated, medication-free Caucasian male war veterans with combat-related PTSD. Veterans had current and chronic PTSD, diagnosed using the Structured Clinical Interview (SCID) based on DSM-IV Disorders. Veterans were categorized according to the presence of pain syndrome into those with or without pain syndrome. The biological and genetic markers were determined from the blood samples using biochemical and genetic analyses. The results, expressed as means &plusmn; standard deviations, were evaluated using one-way analysis of variance, and differences in the genotype and allele frequencies were evaluated using a &chi;2test. Although altered platelet 5-HT concentration was associated with particular symptoms in PTSD, platelet 5-HT concentration was not significantly different between veterans with or without pain syndrome. These results suggest that platelet 5-HT is not a biomarker of the pain syndrome in PTSD. Platelet MAO-B activity, controlled for the smoking status, did not differ significantly between veterans with or without pain syndrome. These data did not confirm the hypothesis that platelet MAO-B might be used as a peripheral marker of the pain syndrome in PTSD. The frequencies of the MAO-B intron 13, DBH-1021C/T, COMT Val158/108Met, BDNF Val66Met, 102T/C 5HT2A, 5HTTLPR variants did not differ significantly between groups of veterans with PTSD with or without pain syndrome, presumably due to the small number of included veterans. In conclusion, our preliminary findings suggest that although combat experience affects the circuits mediating stress response, as well as neural circuitry underlying pain processing, the selected biomarkers, which have been shown to be associated with particular psychopathological symptoms or altered behaviours in PTSD, were similar between groups of veterans with PTSD with or without pain syndrome. These data suggest that further additional studies with larger groups are warranted to shed further light on these associations.