Journal of Pain Research (Jul 2023)
Spinal Excitability in Patients with Painful Chronic Pancreatitis
Abstract
Cecilie Siggaard Knoph,1,2 Rasmus Bach Nedergaard,1 Søren Schou Olesen,1,2 Louise Kuhlmann,1 Asbjørn Mohr Drewes1,2 1Center for Pancreatic Diseases & Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; 2Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkCorrespondence: Asbjørn Mohr Drewes, Center for Pancreatic Diseases, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Mølleparkvej 4, Aalborg, 9000, Denmark, Tel +45 97663562, Email [email protected]: Abdominal pain is common in patients with chronic pancreatitis (CP), but management is challenging – possibly due to altered pain processing within the central nervous system rendering conventional treatments ineffective. We hypothesized that many patients with painful CP have generalized hyperalgesia correlating with central neuronal hyperexcitability.Patients and Methods: Seventeen CP patients with pain and 20 matched healthy controls underwent experimental pain testing, including repeated pain stimuli (temporal summation), pressure algometry performed in dermatomes with same spinal innervation as the pancreatic gland (pancreatic areas) and remote dermatomes (control areas), a cold pressor test and a conditioned pain modulation paradigm. To probe central neuronal excitability, the nociceptive withdrawal reflex was elicited by electrical stimulation of the plantar skin, and electromyography was obtained from the ipsilateral anterior tibial muscle together with somatosensory evoked brain potentials.Results: Compared to healthy controls, patients with painful CP had generalized hyperalgesia as evidenced by 45% lower pressure pain detection thresholds (P< 0.05) and decreased cold pressor endurance time (120 vs 180 seconds, P< 0.001). In patients, reflex thresholds were lower (14 vs 23 mA, P=0.02), and electromyographic responses were increased (16.4 vs 9.7, P=0.04) during the withdrawal reflex, reflecting predominantly spinal hyperexcitability. Evoked brain potentials did not differ between groups. A positive correlation was found between reflex thresholds and cold pressor endurance time (ρ=0.71, P=0.004).Conclusion: We demonstrated somatic hyperalgesia in patients with painful CP associated with spinal hyperexcitability. This highlights that management should be directed at central mechanisms using, eg, gabapentinoids or serotonin-noradrenaline reuptake inhibitors.Keywords: pain, hyperalgesia, nociceptive withdrawal reflex, electroencephalography, electromyography
