Introduction:Chronic low back pain (CLBP) is one of the most common chronic pain conditions in pain practice.Objectives:In the current study, we describe phenotypes of patients with CLBP based on... Show moreIntroduction:Chronic low back pain (CLBP) is one of the most common chronic pain conditions in pain practice.Objectives:In the current study, we describe phenotypes of patients with CLBP based on the status of their endogenous pain modulatory system.Methods:Conditioned pain modulation (a measure of central pain inhibition), temporal summation (TS, a measure of pain facilitation), and offset analgesia (a measure of temporal filtering of nociception) were evaluated in 53 patients with CLBP at painful and nonpainful sites. Next, in a double-blind, randomized, placebo-controlled trial, 40 patients with defective conditioned pain modulation responses received treatment with tapentadol prolonged-release or placebo for 3 months.Results:The majority of patients (87%) demonstrated loss of central pain inhibition combined with segmentally increased TS and reduced offset analgesia at the lower back region. During treatment, tapentadol reduced pain intensity more than placebo (tapentadol -19.5 2.1 mm versus placebo -7.1 +/- 1.8 mm, P = 0.025). Furthermore, tapentadol significantly decreased pain facilitation by reduction of TS responses at the lower back (tapentadol -0.94 +/- 1.9 versus placebo 0.01 +/- 1.5, P = 0.020), which correlated with pain reduction (P < 0.001).Conclusion:Patients with CLBP demonstrated different phenotypes of endogenous pain modulation. In patients with reduced conditioned pain modulation, tapentadol produced long-term pain relief that coincided with reduction of signs of pain facilitation. These data indicate that the endogenous pain system may be used as a biomarker in the pharmacological treatment of CLBP, enabling an individualized, mechanism-based treatment approach. Show less
This thesis describes the evaluation of pain perception in acute and chronic pain patients and the strength of the endogenous pain modulation system in chronic pain patients. Additionally, pain... Show moreThis thesis describes the evaluation of pain perception in acute and chronic pain patients and the strength of the endogenous pain modulation system in chronic pain patients. Additionally, pain phenotypes are determined in patients with chronic pain. The ability of patients with acute pain after surgery and patients with fibromyalgia to consistently score random painful stimuli on a numerical rating scale is assessed, and the influence of opioids on this ability is evaluated. In patients with fibromyalgia, the offset analgesia paradigm is also evaluated. Offset analgesia is defined as the reduction in pain perception after a small decrease in a nociceptive heat stimulus, that is larger than would be expected from the magnitude of the stimulus decrease. This paradigm can be used to assess the endogenous ability to modulate incoming pain signals. Another manifestation of endogenous pain modulation is conditioned pain modulation (CPM). This is the reduction of pain perception of a nociceptive stimulus by the application of a second nociceptive stimulus on a remote area on the body. In this thesis the ability of a new device specifically developed to induce CPM is evaluated. In the last 2 chapters, the signs and symptoms of chronic pain patients with fibromyalgia, diabetes and sarcoidosis are used to construct 4 pain phenotypes. These phenotypes represent groups with more homogeneous patterns of signs and symptoms, which may be important to identify and evaluate targeted drug therapy. Show less
Endogenous pain modulation is a complex phenomenon involved in the perception of pain. It consists of top-down inhibitory and facilitatory pathways that originate at higher sites within the central... Show moreEndogenous pain modulation is a complex phenomenon involved in the perception of pain. It consists of top-down inhibitory and facilitatory pathways that originate at higher sites within the central nervous system and converge at dorsal horn neurons in the spinal cord, to modulate incoming afferent nociceptive information. Dysfunction of inhibitory pain pathways or a shift in the balance between pain facilitation and pain inhibition has been associated with the development of chronic pain. This thesis describes the effect of several central-acting drugs on descending control of pain in both healthy volunteers and chronic pain patients to further understand the underlying mechanism of endogenous pain control in health and disease. Show less
