Common mechanisms of pain and depression: are antidepressants also analgesics?

Neither pain, nor depression exist as independent phenomena per se, they are highly subjective inner states, formed by our brain and built on the bases of our experiences, cognition and emotions. Chronic pain is associated with changes in brain physiology and anatomy. It has been suggested that the neuronal activity underlying subjective perception of chronic pain may be divergent from the activity associated with acute pain. We will discuss the possible common pathophysiological mechanism of chronic pain and depression with respect to the default mode network of the brain, neuroplasticity and the effect of antidepressants on these two pathological conditions. The default mode network of the brain has an important role in the representation of introspective mental activities and therefore can be considered as a nodal point, common for both chronic pain and depression. Neuroplasticity which involves molecular, cellular and synaptic processes modifying connectivity between neurons and neuronal circuits can also be affected by pathological states such as chronic pain or depression. We suppose that pathogenesis of depression and chronic pain shares common negative neuroplastic changes in the central nervous system (CNS). The positive impact of antidepressants would result in a reduction of these pathological cellular/molecular processes and in the amelioration of symptoms, but it may also increase survival times and quality of life of patients with chronic cancer pain.

Assessment of chronic benign and cancer pain using blood plasma biomarkers.

OBJECTIVE: The objective was a systematic study of the biochemical markers which are descriptive for the dynamics of pain processes. MATERIALS AND METHODS: The patients who had not been systematically treated for pain prior to their participation in this study consisted of 20 non-oncological (mean age 56.5 years) and 20 oncological patients (mean age 64.8 years). Pain intensity, assessed using the visual analogue scale (VAS) on a scale from 0-10, and the following biochemical parameters were measured during the initial patient workups: blood serum total protein, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, atherosclerotic indexes, triacylglyceroles, apolipoprotein A, apolipoprotein B, albumin, alpha1 globulin, alpha2 globulin, beta globulin and gamma globulin. Biochemical measurements were repeated as soon as VAS assessments fell below 5. Therapy in non-oncological patients involved administration of NSA and weak opioids; while oncological patients received NSA, medium strength and strong opioids, and antidepressants. RESULTS: Prior to therapy, concentration of albumin in serum, HDL cholesterol, and apolipoprotein A were lower, whereas CRP and alpha1 globulin were higher in oncological patients compared to non-oncological patients. After therapy, levels of glucose and alpha1 globulin were significantly higher and levels of apolipoprotein A were lower in oncological patients compared to non-oncological patients. Irrespective of diagnosis, patients treated with antidepressants showed higher levels of gamma globulin compared to non treated patients. CONCLUSIONS: We can conclude that observed biochemical markers in patients with malignancies are more similar to the values of patients with chronic benign pain than to the values of patients with acute pain.

Assessment of biochemical markers in patients with pain of vascular origin.

The aim of this study was to analyse blood plasma biochemical parameters in patients with pain of vascular origin. Blood samples were taken from 62 patients (38-86 years of age) with critical limb ischaemia, claudication or lower limb embolism, and from a control group. The samples were taken at the time of hospital admission, 1 h after surgery, 24 h after surgery, and before discharge. Pain intensity was assessed as mild, moderate or intense. The following biochemical parameters were measured: C reactive protein, total protein, albumin, total cholesterol, HDL and LDL cholesterol, glucose, triglycerides, reduced glutathione, malondialdehyde (MDA), and total antioxidative capacity. In the control subjects, MDA increased postoperatively, whereas albumin, total protein, HDL and total cholesterol decreased. In patients with claudication triglycerides and LDL cholesterol also decreased postoperatively. In patients with critical limb ischaemia, reduced glutathione and antioxidative capacity decreased postoperatively and MDA increased. Except in patients with embolism, MDA and C reactive protein increased following surgery. Patients with critical limb ischaemia and embolism reported the worst preoperative pain. In patients with ischaemia, intense pain persisted during the whole postoperative period while in patients with embolism pain continuously decreased. At different time intervals, pain intensity was related to different biochemical markers. We suggest that the described blood plasma changes might play an important role in pain assessment and pain management.

Blood serum changes in patients with pain during bone fractures and acute pancreatitis.

OBJECTIVES: Our aim was to evaluate whether some biochemical parameters in the blood serum can establish and discriminate pain intensity of different etiology. METHODS: Three groups of patients hospitalised at the Department of Surgery have been investigated: 1) the patients without pain but with the indicated surgical treatment, 2) the patients with acute pancreatitis, which represents severe pain of the visceral type, and 3) the patients with fractures of upper or lower extremities, which represented acute somatic pain. Whole serum proteins, albumin, C-reactive protein, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglyceroles (triglycerides), apolipoprotein-B and electrophoretic levels of alpha-lipoprotein, beta-lipoprotein and pre-beta-lipoprotein were analysed immediately after the first clinical inspection in the hospital and then 30 days after treatment. RESULTS: The intensity of pain estimated by the visual analogue scale (VAS) was higher in patients with acute pancreatitis than in patients with fractures. In both diagnoses during persisting pain, the products of lipid metabolism such as triacylglyceroles and HDL-cholesterol were enhanced together with glucose levels. Electrophoretic measurements, revealed higher levels of beta-lipoproteins in fractures, and increased values of pre-beta-lipoproteins and alpha-lipoproteins in both groups of patients suffering from pain. After 30 days of treatment some indicators decreased, but when compared with normal values, they were still higher, especially in patients with pancreatitis (HDL-cholesterol, triacylglyceroles, pre-beta-lipoprotein). In control patients without pain symptoms, an increase of LDL cholesterol, triacylglyceroles and beta-lipoprotein were observed during their stay in hospital, which may be considered to be due to hospitalisation stress per se. Acute stress generally influences glucose levels so that their increase cannot be considered as a specific marker of pain intensity. CONCLUSIONS: It may be concluded from our investigation, that the biochemical composition of the blood serum is changing during painful states, although the question still remains open to what extent these changes reflect the pain intensity and to what extent they may modulate the perception of pain.