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 pain in 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 pain and 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)
- 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 enemy.
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.
a) Inflammatory soup containing PGs, bradykinin, Sub P, cytokines. ï¿½ sensitization of afferent nerve terminals.
b) Changes in nociceptors: Active nociceptors become sensitized and sleeping nociceptors awaken. Formation of new nociceptors.
c) Results: Lower activation threshold, increased response to a given stimulus, spontaneous discharge.
2. Damaged axons changes.
a) They sprout, forms collaterals.
b) Ephaptic cross talk between axons (between A-delta & C fibers; Somatic & Sympathetic fibers)
c) 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. 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).
b. Area of pain increases along other nerve distribution.
c. 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:
a. Increased signal transmission
b. 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:
a. Increased intensity of pain.
b. Increased area of pain.
c. Increased duration of pain.
d. Decreased tolerability to pain.
e. Development of psychological problems.
f. pain become non-responsive to conventional analgesics.