1. بسم الله الرحمن الرحيم

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

3. 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.

4. 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.

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

6. 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

7. 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)

8. Analgesic Pathway

9. 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.

10. 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.

11. 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.

12. 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.

13. 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

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

15. Pain Suppression System in the Brain and Spinal Cord

16. 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.

17. 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

18. 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)

19. 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 .

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

21. 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 .

22. THANKS