The Role of Descending Inhibitory Pathways on Chronic Pain Modulation and Clinical Implications

Abstract

The treatment and management of chronic pain is a major challenge for clinicians. Chronic pain is often underdiagnosed and undertreated, and there is a lack of awareness of the pathophysiologic mechanisms that contribute to chronic pain. Chronic pain involves peripheral and central sensitization, as well as the alteration of the pain modulatory pathways. Imbalance between the descending facilitatory systems and the descending inhibitory systems is believed to be involved in chronic pain in pathological conditions. A pharmacological treatment that could restore the balance between these 2 pathways by diminishing the descending facilitatory pain pathways and enhancing the descending inhibitory pain pathways would be a valuable therapeutic option for patients with chronic pain. Due to the lack of evidence for pharmacological options that act on descending facilitation pathways, in this review we summarize the role of the descending inhibitory pain pathways in pain perception. This review will focus primarily on monoaminergic descending inhibitory pain pathways and their contribution to the mechanism of chronic pain and several pharmacological treatment options that enhance these pathways to reduce chronic pain. We describe anatomical structures and neurotransmitters of the descending inhibitory pain pathways that are activated in response to nociceptive pain and altered in response to sustained and persistent pain which leads to chronic pain in various pathological conditions.

Effects of Milnacipran on Clinical Pain and Hyperalgesia of Patients With Fibromyalgia: Results of a 6-Week Randomized Controlled Trial

“…Therefore the test results of both arms were combined and averages used for statistical analyses. 13 10 s ramp and hold pressure stimuli were applied to the supraspinatus muscles, the lateral epicondyles, and the gluteal muscles in counterbalanced order. The mean peak pain ratings (eVAS) for fixed pressure stimuli at the beginning and end of the trial are shown in Table 2 A.…”

“…Besides their effects on negative affect NSRIs are thought to improve chronic pain through central and peripheral nervous systems mechanisms, including noradrenaline and serotonin neurotransmission, actions on opioid, adrenergic, serotonin, GABA and NMDA receptors, ion channel activation and possible effects on inflammatory cytokines 41 . Additionally, they seem to modulate descending inhibitory pain pathways and central sensitization 13,49 .…”

Basic Anatomy and Physiology of Pain Pathways

“…46 The regulation of pain signals transiting through the DH of the spinal cord is also under Basic Anatomy and Physiology of Pain Pathways the control of dopaminergic descending neurons from the periventricular region of the hypothalamus (A11). 47 The dopamine receptor subtype expressed by primary afferents or DH neurons in lamina I dictate an antinociceptive or pronociceptive effect. 47 Dysfunction of this descending pain system may lead to chronic pain conditions; however, this descending dopaminergic system is another potential target for treatment.…”

“…47 The dopamine receptor subtype expressed by primary afferents or DH neurons in lamina I dictate an antinociceptive or pronociceptive effect. 47 Dysfunction of this descending pain system may lead to chronic pain conditions; however, this descending dopaminergic system is another potential target for treatment. 47 The descending endogenous opioid pain modulation system also augments pain processing.…”

Experimental pain sensitivity in women with vestibulodynia: a pilot study

“…These pathways arise in multiple areas of the cerebrum and brainstem and inhibit transmission of nociceptive inputs at the level of the dorsal horn. 16 Obviously, it is difficult to draw conclusions with a sample size of one and this patient could very well be an outlier, or simply be evidence that baseline pain is not predictive of evoked pain sensitivity.…”