Buy Fgxpress Powerstrips or Solarstrips ONLINE
After tissue damage following any kind of injury there is release of membrane Phospholipids. By the action of enzyme PhospholipaseA2 this is converted to Arachidonic acid. It again is converted to Prostaglandins (PGs) by the action of Cyclooxygenase or COX. These PGs and other chemical mediators like bradykinin, subP serotonin, histamine, potassium and hydrogen ions sensitize A delta & C fibres (they are pain bearing nerves). So they are up regulated & impulse is easily generated and carried to the dorsal horn of spinal cord. There they synapse with cells of the spinothalamic tract, which carry the impulses up the spinal cord, through the brain stem to the thalamus. From the thalamus, impulses are delivered to various areas of the cerebral cortex that allow the perception of pain and reaction to pain.
In the dorsal horn of the spinal cord the afferent sensory nerves synapse with fibres of the ascending spinothalamic tract, either directly or via a complex system of connecting fibres or interneurons, employing a variety of neurotransmitters that include substance P and glutamate. The presynaptic terminal of the afferent sensory fibre contains opioid receptors which bind endogenous opioid substances (endorphins) or exogenous opioid medications. Such binding reduces or blocks the release of neurotransmitter by the afferent sensory fibre, reducing or relieving the sensation of pain. This is the prime site of action of exogenous opioid drugs. Similarly, activation of the inhibitory neurons in the dorsal horn, known to have endorphins as neurotransmitters, will reduce pain. The inhibitory neurons are stimulated by activity in the descending pathways from the brain or by activity in other sensory fibres in the same segment, explaining why massage, heat or electrical stimulation applied to a painful area may reduce pain. Other receptors in the dorsal horn may have an opposite effect. Activation of the N-methyl D-aspartate (NMDA) receptors sensitizes dorsal horn cells & will facilitate/perpetuate the sensation and may responsible for the reduced opioid sensitivity of neuropathic pain. The NMDA receptor antagonist, ketamine, can be effective in relieving pain in this situation.
Pain impulses transmitted to the thalamus are relayed to several areas of the cerebral cortex: the sensory areas of the parietal lobe that allow localization and interpretation of the pain; the limbic system, which is involved in both the affective and autonomic response to the pain; the temporal lobe, which is involved in pain memory; and the frontal lobe where cognitive function assesses the significance of the pain and the emotional response to it.
The major endogenous mechanism of pain inhibition is the suppression of pain impulses at the dorsal horn by pathways descending from the midbrain and brain stem. These centres receive input from the cortex, the thalamus and other midbrain centres and, by a variety of descending pathways, stimulate the inhibitory interneu�rons in the dorsal horn of the spinal cord, producing analgesia or reducing pain. The neurotransmitters involved with the descending inhibitory pathways are noradrena�line and serotonin. This is a possible explanation as to why drugs that block presynaptic re-uptake and augment the postsynaptic action of these substances, such as amitriptyline, may augment analgesia.
Neuropathic pain results from anatomical and/or physiological changes which may be due to damage to nerves or neural tissue rather than the stimulation of nociceptors by tissue injury or inflammation. Pain results from spontaneous electrical activity of the damaged nerves or to increased sensitivity to exogenous stimuli; the neural pathways involved are the same as for nociception. Damage to sensory afferent fibres results in a significant reduction in the number of opioid receptors in the presynaptic terminals of the affected fibres in the dorsal horn, possibly explaining the reduced opioid sensitivity of neuropathic pain. Damage to sympathetic nerve fibres may lead to sympathetic type pain in which neuropathic pain is accompanied by signs of autonomic dysfunction, including vasomotor instability and sudomotor (sweating) changes.
Chronic pain: a symptom or a disease?
Pain has been defined by International Society for Study of pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage." Note the last few words, even in the absence of actual/potential tissue damage if a person describe unpleasant sensation in terms of actual/potential tissue damage it is called pain. Take the example of Phantom limb pain. Here patient feel painin the limb which is not there; so question of tissue damage does not arise. Till 1960s doctors thought it was due to psychological problem but now we know the exact pathophysiology of pain, which is a real painand not psychological. Similarly in lumbago, sciatica, CRPS, fibromyalgia etc. there are definite pathophysiological problem in the nervous system which can be reversed with interventional pain management. It is now definitely proved that with a few exception like Rheumatoid arthritis in all chronic pain there are problems in the nervous system and so Chronic pain can be called a disease itself.
painmay be broadly divided into two types:
Acute pain( may be called Physiological Pain)
? Nociceptive
? It is a symptom of a disease
? Treatment of diseases cures pain& it is self-limiting.
? It is proportional with tissue damage & correlates with clinical finding
? It is an alarm of a disease and is our friend.
Chronic pain(may be called Pathological Pain)
? Non-nociceptive, may be Neuropathic
? It is disease itself, a disease of nervous system.
? Difficult to treat & sustaining.
? It is disproportional with tissue damage & does not correlates with clinical finding
? It is a false alarm and is our enimy.
Definition of Chronic Pain:
Chronic pain has been defined in many ways. American chronic pain association defines it as pain that continues a month or more beyond the usual recovery period. Some has described chronic pain as pain persisting more than 3 months, some by 6 months. In other way all pain is acute pain till it becomes chronic pain. But sensitization is the constant feature in all types of chronic pain.
Sensitization is a phenomenon of inappropriate or disproportionate response to normal stimulus. Sensitization outside central nervous system (CNS) is called Peripheral sensitization and that in the CNS is called Central sensitization.
PERIPHRAL SENSITIZATION: Here there are following changes:
1. Sensitization of primary afferent terminals.
? Inflammatory soup containing PGs, bradykinin, Sub P, cytokines. � sensitization of afferent nerve terminals.
? Changes in nociceptors: Active nociceptors become sensitized and sleeping nociceptors awaken. Formation of new nociceptors.
? Results: Lower activation threshold, increased response to a given stimulus, spontaneous discharge.
2. Damaged axons changes.
? They sprout, forms collaterals.
? �Ephaptic cross talk� between axons (between A-delta & C fibers; Somatic & Sympathetic fibers)
? Increased density of abnormal Na-channel & Ca-channel leading to ectopic discharge.
3. Ectopic discharges along nerve axon, terminals & at Dorsal Root Ganglion (DRG).
4. Sympathetic Nerve fibers invade DRG.
5. Phenotypic switch in expression of neuropeptides like Sub P, CGRP.
CENTRAL NENSITIZATION : changes are following:
1. Central Reorganization. When these signals (for pain) are powerful & long continued they release some oncogenes in the dorsal horn. They are c-fos & c-jun. They in turn release neuropeptides in the spinal cord, which alters anatomy and physiology of nervous system. These changes are called central reorganization. They are as follows:
? A-beta fibres (carrying touch sensations and normally ends in the deeper lamina of spinal cord) develop connections in lamina 2 where pain-carrying fibres normally ends. This leads to Allodynia (touch causes pain sensation).
? Area of pain increases along other nerve distribution.
? Loss descending inhibitory pathways
2. Wind up (summation of signals): Repeated activation of dorsal horn cell by strong and /or sustained noxious stimulus leads to increased excitatory response of these cells.
3. Up-regulation of NMDA receptor
Acute pain ? AMPA receptors stimulated ? dislodges Mg from NMDA
receptors??activation of NMDA receptors. Activation of NMDA receptors leads to following changes:
? Increased signal transmission
? Release of NO, sub-P & PGs
4. Ectopic activity
5. Depression inhibitory synapses
6. Activation of Wide Dynamic Range cells.
All these leads to following clinical changes:
? Increased intensity of pain.
? Increased area of pain.
? Increased duration of pain.
? Decreased tolerability to pain.
? Development of psychological problems.
? pain become non-responsive to conventional analgesics.