بسم الله الرحمن الرحيم

Physiology of Pain Modulations Dr. Mohammed Moizuddin Khan MBBS, MD, PhD Associate Professor

Objectives Upon completion of this lecture, students should be able to: To know various extrinsic and intrinsic mechanisms of pain modulation Describe how endogenous opiates may modulate the pain experience & pain can be modulated by giving analgesic drugs e.g. morphine. Clarifies the concept of dorsal horn mechanism of gating pain.

Brain Analgesia System Brain has built in analgesic system. By sending message through descending analgesic pathway to the inhibitory neuron in the Dorsal horn cell of spinal cord. Brain descending pathways release Enkephalin which bind with opiate receptors at afferent pain fiber terminals in Dorsal horn of spinal cord and work like Morphine (powerful analgesic). Endorphin, Enkephalin and Dynorphin are endogenous or natural analgesic system. They suppress release of substance P.

Components Periaqueductal grey and periventricular areas Nucleus Raphe Magnus Pain Inhibitory complex located in dorsal horn of Spinal cord

pre & postsynaptic inhibition The latter projects serotoninergic pathways to inteneurons which synapse with the first-order neurons of the pain pathway. These release encephalins and pain transmission is inhibited by both pre- and postsynaptic inhibition. pre & postsynaptic inhibition

Central Inhibition of Pain Examples: Pain perception vary in each individual Inhibition of pain transmission by simultaneous tactile sensory signals Stress analgesia. Acupuncture Irritation of skin overly disease viscera relive pain (Mustard plaster) Inhibition of Pain Transmission by simultaneous tactil sensory signals (rubbing over an injured area often reduce pain)

Analgesic Pathway

GATE CONTROL THEORY OF PAIN The dorsal horn of spinal cord , in particular the neurons of substantia gelatinosa, form the gate through which pain impulses must pass in order to reach the brain. Impulses coming along the C fibers cause the release of substance P & open the “gate” in the dorsal horn. Glutamate is a neurotransmitter released by A-delta fiber at the dorsal horn cell.

GATE CONTROL THEORY OF PAIN Impulses coming along the large diameter Aβ fibers close the “gate” at the dorsal horn. The “gate” is also under control of higher centers in brain, by means of analgesic system of corticospinal & reticulospinal fibers.

Other Factor That Modify Pain Exercise, Stress modify pain. How they work? By release of Endorphin. How ACUPUNCTURE works for pain? By release of Endorphin, Endogenous opiates & neurotransmitters like serotonin, Norepinephrine, Cortisol.

Phenomena of modified pain sensation Hyperalgesia Is an exaggerated response to a noxious stimulus. Primary hyperalgesia: Excessive sensitivity of the pain receptors, from sensitization of the skin pain endings by local chemicals (histamine, prostaglandins, …) ↓ threshold of stimulus e.g. extreme sensitivity of sun burned skin. Secondary hyperalgesia : Facilitation of sensory transmission, results from lesions in the spinal cord or the Thalamus.

Bumping the head The initial trauma activates the A-delta & eventually, C fiber Rubbing the traumatized area stimulates the A-beta fibers, which activate the SG to close the spinal gate. Thus inhibiting transmission of the painful stimulus

Other clinical e.g. : Electrical transcutaneous stimulation of peripheral nerve Implantation of dorsal column stimulator. Stimulate Large Aβ fiber

Pain Suppression System in the Brain and Spinal Cord

Endogenous Opiate stresses, sexual stimulation, placebos acupuncture. Two naturally secreted morphine-like compounds in the brain: Endorphins 2. Enkephalins Endogenous opioids are released by a variety of stimulants include: pain stresses, sexual stimulation, placebos acupuncture.

Enkephalin Are a group of naturally occurring peptides found in high concentrations in the periaqueductal grey matter. acting on opioid peripheral & central receptors Mechanism of action of Enkephalin: Opioid Receptors Peripherally In afferent fibers Opioids released by immune cells during inflammation

Endorphins Another group of peptides that abundant in the hypothalamus and pituitary. Proved to prevent withdrawal symptoms in opium addicts. Increase during labor (body’s self analgesic system)

Treatment of pain Treat the cause!! e.g. : ischemic pain (vasodilator). peptic ulcer (antacids + anti-ulcer drugs. Use analgesia: NSAID Large fiber stimulation e.g. hot water bottle . - mustard plaster . - cutaneous electrodes . - dorsal column stimulators .

Treatment of pain??? Local anesthesia Electrical stimulation of periaqueductal grey matter . Surgical denervation Psychotherapy.

Acupuncture : Mode of action : Acupuncture at a location distant from site of pain acts by releasing endorphins . Acupuncture at the site of pain acts by stimulating large myelinated fibers .

THANKS