Pain is an unpleasant sensation with no specific stimulus and depends on individual's tolerance.

PHYSIOLOGY:

Transduction ( receptor activation )

It is the conversion of one form of energy, (thermal, mechanical, or chemical), into a form that is accessible to the brain (nerve impulse). The exact mechanism is not known, but a number of mechanical and chemical interactions are known to influence activity in primary afferent nociceptors at the free nerve endings of the primary afferent fiber.

These nociceptors can be divided into 1. A-delta 2. C-fiber

These fibers are also responsible for deep pain (muscle & joints) as well as visceral pain although not much is known about them.

In addition to noxious stimuli, nociceptor can become sensitive to variety of chemical factors present after a local injury.

The size, site stimulated, the frequency with which stimuli applied and the duration of the stimuli and the chemical changes at the site will interact to produce the nerve impulse.

Transmission:

Neural impulses thus produced are carried along the peripheral nerves, nerve roots, spinal cord, brainstem, thalamus and the cortex that ultimately leads to an awareness of pain.

The majority of primary afferents- project to the spinal cord through dorsal root. At the ventrolateral aspect of the dorsal root A-delta and C fibers segregate and enter the spinal cord. Some may project to the spinal cord through ventral root.

Recent studies suggest, they loop back and enter along the dorsal root. In the spinal cord, the fibers become part of Lissaur's tract which is located at the dorsolateral edge of the spinal cord and divide into ascending and descending branches that extend for one or two spinal segments.

Spinal cord grey matter is organized into ten laminae (REX) C-fibers project mainly to I and II laminae and A-delta to I to V. The neurons in the cord can be divided into projection neurons (relay to higher centers), excitatory neurons (relay to projection and other interneurons or to motor neuron that mediate spinal reflexes) and inhibitory interneurons (contribute to the control of nociceptive transmission). Laminae I, V, VII, VIII are the major sources of rostarlly projecting nociceptor neuron. Laminae II (substantia gelatinosa) make predominantly local connection that result in important changes in the neuronal activity.

Among Nocicecptive Transmitters involved in the cord, substance P is well known and found in dense concentration in laminae I and II and in many dorsal root ganglion cells. Other substances are somatostatin, vasoactive intestinal polypeptide, glutamate, aspartate and adenosine triphosphate.

Gate Control Hypothesis suggests interaction between myelinated and nonmyelinated neurons occurs at inhibitory interneurons in substantia gelatinosa and at dorsal horn. The myelinated afferents said to excite inhibitory interneurons and inhibit pain. The nonmyelinated nociceptors inhibit the inhibitory interneurons. The perceived intensity is the net effect. Although current evidence suggest that it is incorrect, transcutaneous electrical-neuron stimulator (TENS) is developed on this. The major spinal pathways for pain travels in the anterolateral spinal quadrant to the thalamus (spinothalamic tract) and crosses over to the other side 2 or 3 segments above. Certain proportion of pain impulses can be carried in ipsilateral pathway.

The Spino Thalamic Tract divides into

(a) lateral division which terminates in posterior nuclear group and ventrobasal nuclei (VPM & VPC). The major projection is from I & V laminae with receptive field restricted to one side of the body usually part of a limb

(b) medial division is called paleo spinothalamic tract and terminate in the central lateral nucleus. The major projection is from entire body surface.

(c) Spino reticular projection appear to involve V,VI VII & VIII laminae and have complex receptive fields from both sides similar to paleo spino thalamic tract.

Thalamic Nuclei project to somoto sensory of cortex (lateral spino thalamic tract). and limbic and frontal lobes (medial and reticulo thalamic). SSC ( somato-sensory cortex )is involved in to localization and identification. Limbic system and frontal lobe responsible for emotional aspects suffering and anxiety.

Modulation:

The process by which the nervous system modifies the nociceptor activity is called modulation. The modulatory network is quite different from sensory system and involves a number of brainstem regions (periaquenductal grey and immediately adjacent midbrain, periventricular grey of hypothalamus, the lateral and dorsolateral pontine tegmentum and rostro ventral medulla). Stimulation of any of these sites reduce pains and inhibit nociceptive neurones. Both nor adrenergic and serotonerigc systems are involved. In addition these produce endogenous opiod peptides which are at least partially responsible for analgesia. The opiod peptides are

(1) Enkephalin (most extensively distributed)
(2) B-Endorphrin (most potent)
(3) Dynorphin similiar to enkeplin and less extensively distributed.

This modulatory system project to the spinal cord along the dorsolateral funiculus. It doesn't work when there is no pain.

In summary, pain involves a complex interaction. Modification occurs at the spinal cord with interneurone and descending modulatory network. Transmission to higher levels occur through spino thalamic and reticulo thalamic tract to SSC and limbic system and frontal lobe. The sense of pain is the net result of all these.

MANAGEMENT:

Acute pain is an alerting or useful pain, signifying tissue injury from a medically or operatively remediable somatic cause, often accompanied by signs of autonomic hyperactivity.

Chronic Pain, however persists beyond the period of what was believed to be curative treatment. The typical pattern involves about six months of use of serial monotherapies, attempting a 'cure' but yielding only partial and numerous exacerbations. Patients quickly develop tranquilizer tolerance and dependence with increasing risk of organ damage and accelerating chronic pain behavior. The chronic pain may be cancerous and noncancerous.

Certainly, patients with Cancer Pain will have different psycho social factors operating. However, approaches applied for the pain can and should be the same for both types with obvious addition of appropriate testing to rule out recurrent disease and of more aggressive neuro surgical ablative techniques for patient with cancer pain and a limited life expectancy.

1 ) Evaluation of chronic pain:

1. History will usually give a clue to the initial triggering factor (injury, operation) and site of nociception. Deafferentation components (, burning pain) can evolve from initial neuritic dysfunction and present as 'new pain'. Numerical value to pain or to mark the current severity of the pain on a 10cm line help in reassessment.

2. Physical exam should include complete survey of baseline sensory motor, circulatory and skeletal parameters. In addition, a search for tender scars, region of vascular entrapment and trigger points should be made.

3. Imaging and electrical studies will help in doubtful cases.

4.Formal psychological evaluation is often sought in a multi disciplinary pain management. Psychological tests (Minnesota multi phasic personality inventory, beck depression scale) help treatment planning.

2 ) Medications:

Analgesics should be prescribed as round the clock medication to be effective and decrease the total drug required. Simpler drugs (aspirin) should be maximized before switching to stronger alternatives. Adjunctive drugs include those specific for the etiology (eg., Phenytoin, carbamazepine of trigeminal neuralgia, NSAID or muscle relaxants for chronic soft tissue and muscle changes). Pain modulation may be stimulated by tricyclic antidepressants (amitriptyline or doxepins 100-200mg at bed time). Patients who require narcotics should be carefully followed up. Withdrawal should be slow. The narcotics can be abruptly discontinued and clonidine may help with drawl signs and symptoms if required.

3 ) Non pharmacological techniques:

a. Psychological techniques such as hypnotherapy, meditation, stress management techniques, relaxation training or bio feed back will help.

b. Rehabilitation should be included in all treatment plans. Occupational therapy and vocational rehabilitation may also be appropriate.

4 ) Neurosurgical intervention:

A survey revealed that only 3 to 10% of the patients referred to general pain clinics for pain other than that of malignant disease were treated by invasive neurosurgical intervention and of this 50% obtained satisfactory relief.

Non specific procedures are divided into two groups :

1. Stimulation procedures depend on blocking pain pathways or reversible stimulation of inhibitory pathways and do not ordinarily result in destruction and hence are reversible.

2. Destructive lesions or ablative procedures deprive the patient of pain and possibly of other sensations and not reversible. Decision making involves assessment of the risk to benefit ratio. Many ablative procedures do not work in the long run and do not have a place in non malignant chronic pain. Generally, the higher the lesions, the less likelihood for permanent relief, so that the most peripheral procedures are considered first. Although stimulation procedures do not necessarily result in permanent dysfunction, greater risk is associated with some than with others.

Stimulation procedures:

1. Transcutaneous Stimulation in which a controlled electrical stimulus to the skin is a popular one with about 50% success rate regardless of cause of pain and various battery operated kits are freely available. According to gate theory when large myelinated fiber activity is increased by non painful stimulus, the pathway for non-myelinated small fibers transmitting pain is closed. Rubbing an injured part similarly reduces pain.

2. Peripheral Nerve Stimulation is similar to above with electrode around the individual peripheral nerve in neuropathic pains confined to a single nerve.

3. Dorsal Column Stimulation applies a train of electrical stimuli to the dorsal aspect of the cord by means of an apparatus that can be controlled by the patient. This attempts to stimulate the collaterals of the large fibers as they ascend in the dorsal column, resulting in increasing the rate and inhibits perception of pain. Percutaneous insertion allows a trial. If there is satisfactory result, a laminectomy is done and electrodes are placed in sub dural / sub arachnoid space and connected subcutaneously to a receiver placed subcutaneously at a convenient location. Patients control the stimulus by adjusting battery operated radio transmitter that they carry.

4. Deep Brain Stimulation is an outgrowth of the above and still an investigational procedure, despite the development of steretactic procedures. The internal capsule, ventral posterior nuclear complex are the usual targets. This helps in pain secondary to cord lesions, thalamic syndrome, or phantom limb pains. Periventricular or periaqueductal grey is a recent target and related to endogenous opiate analgesia.

Ablative procedures:

Peripheral Nerve Blockade:

It is of limited value, but easily available, also serve to test the possible result of permanent denervation.

Posterior Spinal Root Blockade: 

Judicious amount of phenol or ethyl alcohol into the spinal subarachnoid space would damage the adjacent sensory rootlets sufficiently to block afferent impulses for several months. Subarachnoid injections are most effective from the low thoracic level. At higher levels, some prefer extradural injections. Depending on the concentration and duration of exposure, phenols could cause reversible or irreversible block. Immediate effect is that of a local anesthetic. The permanent effects are due to degeneration. Long acting steroid (Depomedrol) is often used these days along with local anesthetics especially in chronic pain of radicular origin.

Posterior Rhizotomy:

If the course of pain can be accurately delineated by segmented boundaries and is limited to few divisions, rhizotomy should provide permanent relief. Such conditions include traumatic lesions of peripheral nerves, operations scars, intercostal or occipital neuralgias. Unfortunately the results are unpredictable because of wandering root filaments, and segmental overlaps. It is recommended that at least, 3-5 adjacent roots and dorsal root ganglia are excised.

Anterolateral cordotomy:

Extremely useful in cancer pain.

Open cordotomy: Usually performed at one of the two levels, the T3 for pain below midthoracic level and C1-2 for pain above the mid thoracic. Surgical observation show that to obtain the maximum benefit, it may be necessary to extend the cordotomy virtually to the midline anteriorly and to include all the distal segments it is necessary to extend it a millimeter or so posterior to the attachment of ligamentum denticulatum. Division of and the traction on the ligamentum denticulatum will usually provide sufficient access. Division of adjacent posterior root will afford greater mobility.

Complications:

1. Respiratory Failure: Most likely in those with low pulmonary efficiency, for variety of reasons. Bilateral procedures at the same session is likely to prove dangerous. Persistence of pharmacological respiratory depression due to prolonged pre op narcotics may be possible cause. It is recommended to stop such drugs two days before the procedure.

2. Hypotension: Sudden drop in BP is often recorded immediately after incision in the spinal cord, most severe and protracted in bilateral procedures. Sympathetic disturbances is blamed.

3. Disturbed sphincter control and paresis as in any spinal procedure, especially in bilateral procedure.

4. Dysaesthesiae:

a) Soreness at about these segmental levels of the cordotomy with girdle distribution. It tends to be temporary.

b) Below the level is often more serious. It is usually delayed. It emerges on simultaneously with return of sensation and may take the form of tingling, pins and needles or other sensations. These abnormal sensations are more likely related to disturbances of the pattern of ascending impulses.

c) Referred sensation to the opposite side which is poorly localized, may be due to the disease process and this pain was not appreciated by the patient because of the intensity of pain in the area of complaint. This referred pain may warrant bilateral section.

5. Recurrence: It may be due to insufficient spinothalamic fibers have been divided but repeat procedure does not help. Other possibility is the regeneration of fibers. The other & more likely possibility is the development of alternate pathways.

Percutaneous cordotomy  requires a cooperative patient and specialized equipments and is recommended for unilateral pain. It involves physiological localization in an awake patient and graded radio frequency electrical destruction of the tract. Complications are less often

Dorsal root entry zone (DREZ) cordotomy:

A destructive lesion is created in the postero lateral sulcus of the spinal cord at the point of entry of the dorsal roots. Ideally R. F. lesioning is made under radiographic control. Some advocate laser lesions. DREZ lesions are designed to destroy regions of neuronal dysfunction in deafferentation states involving particularly Lissauer's tract and I,II & V Rex layers. These areas show increased neuronal activity in experimental deafferentation models. DREZ lesions help in deafferentation pain such as causalgia, root avulsions, herpetic neuralgia etc.

Commisural myelotomy:

The spinothalamic fibers can be interrupted as they cross the ant. commissure by a vertical incision in the median plane. The result is bilaterally symmetrical area of analgesia. This procedure is not widely accepted.

Spinothalamic tractomy in the brainstem:

Medullary, pontine, mesencephalic tractomies have been described. Due to high mortality and morbidity, they never became popular. Stereo tactic techniques have also been tried. It may have a role in cancer pain involving the head and neck.

Sympathectomy:

Repeated temporary anesthetic blockade should proceed symphathectomy - causalgia, sympathetic dystrophy and painful ischemic states are the main indications. It is also helpful in visceral Ca. Open sympathtectomy has been replaced with per cutaneous method using R.F . lesioning, phenol injections and endoscopic techniques.

A localized type of sympathetic block with I.V.guanethidine which displaces norepinephrine the neurotransmitter at the sympathetic nerve endings and occupies the storage sites. When it is given I.V.. with proximal tourniquet, the storage applied for about 20 minutes, Guanethidine is fixed to the tissues and it abolishes sympathetic activity locally.

Phenoxy - Benzamine (adrenergic receptor blocker) is given orally at frequent intervals for about six weeks and then tapered off. This reportedly gives equal results.

Stereotaxic thalamic lesioning:

This involves lesioning thalamic nuclei and hence disturbs nociception. There is a shift of stereotaxic lesions away from ventral lateral (specific) nuclei to the ventral posterior medial and interlaminar (nonspecific) nuclei. Since the introduction percutaneous cordotomy, the thalamotomies have became rare.

Pituitary destruction:

For pain associated with advanced Ca breast and prostate, pituitary destruction was once a routine treatment. Open Hypophysectomy, transphenoidal percutaneous radio frequency coagulation and other techniques have been reported with about 75% pain relief. But the relief lasts for only few months. The mechanism of pain relief is not understood, it may be related to hormones.

Operations on the cortex and subcortex:

The aim is to create lesions deep to secondary sensory are which severs its links with thalamus. Leucotomy was once practiced. Stereotactic cingulomotomy and infero medial quadrant frontal section have proved helpful. All aim to disturb pain perception.

Conclusion:

Pain may be classified into 'normal' pain and abnormal pain.

'Normal pain' is due to nociceptive stimuli such as scar, arachnoiditis, malignant infiltration or any such demonstrable lesion. When such lesion cannot be treated effectively and conservative measures have failed, surgical intervention such as nerve blockade, intrathecal injection, peripheral neurectomy, dorsal rhizotomy and cordotomy. Unlike others. cordotomy abolishes only pain sensations and preserve other neural functions.

'Abnormal Pain' include

Hyperalgesia (normal painful stimulus produce abnormally severe pain),

Allodynia (gentle touch cause intensive pain),

Hyperpathia (pain threshold is increased but once reached it causes intense pain),

Causalgia (above with features of sympathetic dystrophy such as shiny skin and tropic changes) are due to abnormal transmission '(deafferentaion) and DREZ is a popular procedure.

Long standing normal pain may become associated with abnormal pain, compounding your problem and resulting in failure.