Pain Clinics have an important role to play in the health care systems of the developing countries and cater to a very large number of chronic pain patients including those with intractable cancer pain. The pain clinicians in these countries have the dilemma of providing the best pain treatment but within the resources available for the purpose. Keeping pace with the technological advances in pain management worldwide, pain clinics in developing countries are also employing newer methods of pain assessment, pain imaging and advanced interventional strategies for managing patients with chronic pain. The multidisciplinary approach to the management of pain at these centres includes the effective use of both the traditional modalities such as yoga and acupuncture as well as the advanced interventional pain management techniques such as dorsal column stimulation, radiofrequency lesioning and implantation of the Intrathecal drug delivery systems.

Continuous intrachecal opioid administration for intractable malignant as well as non malignant pain by using implantable pumps has been in vogue since early 1980?s. Owing to a very high cost of those pumps, the literature refers to reports from developed countries only. It has also remained the domain of neurosurgeon to surgically implant these pumps in patients with intractable benign or malignant pain. Now with the explosion of information technology and integration of developing world economy with developed world economy, these high technology advanced interventional modes of therapy are available in developing counties also. More so with greater involvement of Anesthesiologists in the management of Chronic Pain and having extensive experience in handling opioids systemically as well as for neuroaxial blocks worldwide, more and more of there devices are implanted and regulated by Anesthesiologists alone.In this lecture ,I will present our experience of using the implantable drug delivery systems for management of benign and malignant pain as well as for managing spasticity.

The discovery of opioid receptors and endogenous opioid compounds in the spinal cord provided a rationale for delivering opioid drugs intraspinally. With a growing experience with "selective spinal analgesia" using intrathecal opioids, continuous subarachnoid opioid infusion using implanted pumps with factory preset flow rates was extensively tried. However, during the last decade a number of reports have confirmed the safety and efficacy of implanted programmable and non programmable pumps for long term subarachnoid delivery of opioids for management of cancer and intractable benign pain including neuropathic pain. Nociceptive Pain producing chronic pain states are more responsive to opioid infusions as compared to neuropathic pain which may be less responsive or may require higher doses than those used for nociceptive pain. Neuropathic pain syndromes may however respond to other intraspinal agent such as clonidine, midazolam or even low concentrations of local anaesthetics.

Indications of Intrathecal Drug Delivery Systems

Intrathecal Opioids for Pain Relief

In general, intraspinal pain therapy using implantable drug administration systems has been reserved for patients whose condition is considered chronic. This technique is not indicated for acute pain syndromes. Chronicity may be defined in terms of time (e.g., pain lasting longer than 3 or 4 months that is inadequately relieved by standard medical management.) Chronicity may also be defined in terms of pain present more than 1 month beyond what a normal healing process would be expected to take.

With regard to cancer-related pain, although the disease is progressive, if the pain is expected to last beyond 3 months, it can be thought of as chronic. The indication for use of implantable drug administration systems then includes the treatment of chronic pain of both cancer related and non cancer related varieties.

Before implantation of a system for delivery of intraspinal analgesics, a trial with the agent that are intended for longterm use is mandatory. Trials help in verifying the analgesic efficacy and also rule out the toxicity of the agent to be used. Trial may be performed either epidurally or intrathecally and are usually done by placing catheters and infusing the selected opioids over some period of time.

Intrathecal Baclofen in the Treatment of Cerebral and Spinal Origin Spasticity

Intrathecal baclofen therapy, which is nondestructive, titratable, reversible, and associated with fewer CNS-related side effects than the oral medication was approved by the US Food and Drug Administration (FDA) for treatment of cerebral origin spasticity in June 1996. It provides an excellent alternative to oral treatment and/or orthopaedic surgery for cerebral or spinal origin spasticity. Intrathecal baclofen can be used to improve the patient?s range of motion, facilitate movement, reduce energy expenditures, facilitate both self care and nursing, reduce the risk of developing contractures, and diminish pain resulting from spasticity and/or spasms. Some reports indicate that ITB treatment results in improved speech, gait, upper extremity function, and activities of daily living, including communication, eating, dressing and hygiene , ITB reduces upper and lower extremity spasticity, which can some times facilitate the use of communication devices. Some patients report increased endurance, as well as improved ability to tolerate ankle foot orthoses and to sit comfortably in the wheelchair or scooter. Because ITB is titratable and reversible, it allows a particular decrease of spasticity with concomitant savings in spasticity related functions something often not possible with the irreversible "all or nothing" effect of neuroablative techniques. Although ITB therapy requires a surgical procedure with associated risk of complications, as well as long term maintenance, its potential benefits make it an excellent treatment option.

Inclusion Criteria

Nociceptive/Neuropathic Pain - Benign or Malignant

Spasticity -Central or Spinal in origin

Demonstrated opioid/baclofen responsiveness

No untreated psychopathology that might predispose to an unsuccessful outcome.

Successful completion of a secreting trial.

Equipments Required

Implantable externally programmable intrathecal infusion pump.

Intrathecal catheter set

Appropriate surgical instruments for implantation.

Continuous intrathecal morphine and baclofen administered by an implanted programmable SynchroMed Infusion System, is a safe and clinically effective method of treating intractable benign and malignant pain as well as spasticity arising from traumatic brain injury or cerebral palsy. Reduction of spasticity can result in functional improvement, alleviation of pain, and ease of care.

Are Epidural Steroids Useful? Dr (Prof) G P Dureja Injections of steroids into the lumbar epidural space are frequently used for low back and related radicular leg pains. The question is do they work? The answer: It depends on whom you ask. The controlled studies are split. Two major problems complicate the story. The first is that many different diagnoses may cause the pain, and epidural injections may work for some of these diagnoses better than others. The second problem is that the success of the injection may depend on the technique that is used. The traditional epidural injection technique involves the doctor feeling the patient’s spine in order to guide the placement of a needle between the spinal vertebrae. A newer technique involves using x-ray fluoroscopy to guide the needle directly to the neural foramen, the point where the affected spinal nerve root exits the spine. This is likely to increase the success of the procedure, but a controlled study using such injection techniques has not yet been done. However, a study in the Archives of Physical Medicine & Rehabilitation did give added support to this idea. 75% of the 69 patients treated with these more precisely placed injections demonstrated good long-term benefit. For patients with nerve root pain involving one or two roots, I believe that fluoroscopically guided foraminal injections will prove to be superior to the approaches that do not use x-ray guidance. Epidurals in general, but especially foraminal injections, do not appear to be as effective if the pain is caused by widespread degenerative or arthritic problems in the spine. Do epidural steroid injections work? Yes, if the problem is back and leg pain triggered lumbar disc herniations, and if fluoroscopy is used to guide the injection directly to the affected nerve roots. Do epidural injections work for other causes of back pain? Good data is not available. In my experience, the injections can often help, but with other diagnoses the rate of success is not as great.

Pain is usually not an early sign of Gynaecological malignancies but is associated with advanced pelvic cancers in about 75% of cases, presumably because of their tendency to spread locally by direct invasion or metastasis to regional lymph modes .pain is a common complaint in carcinoma cervix and carcinoma of body of uterus.However ,occurrence of pain is a late symptom in cancers of ovaries,vulva and vagina.

Severe pain in advanced gynaecological cancers occurs because of various factors such as tumour infiltration of the pelvis, involvement of lumbar plexus as in uterine cancer, bony metastasis in spine and pelvic bones, massive ascitic fluid distending the abdomen and infiltration of peritoneum and viscera. Pain may also be due to pressure or traction on pain-sensitive structures, obstruction of lymphatic and vascular channels, distension of hollow organs, and localized edema, inflammation, and necrosis.In one series, pain was most commonly referred to the rectum, where it tended to be characterized either as "fullness" or "shooting like a red-hot poker," suggesting an underlying visceral versus neuropathic mechanism. Pain may also be experienced in the low back, hypogastrium, and perineum and may be most troublesome when it is associated with destruction of the sacrum.

Assessment of pain
Assessment of pelvic pain caused by gynaecological neoplasm`s is often difficult because it is characteristically vague and poorly localized.The assessment involves localising the cause of pain which may involve radiological investigations such as MRI,CT scans and Bone scan.The severity of pain is quantified using a visual Analogue Pain Scale(VAS) which is important for deciding the pain treatment modality.A behavioural assessment is also done to assess the emotional and affective component of pain due to cancer.

MANAGEMENT of PAIN
Primary treatment involves modifying the source of pain with surgery, chemotherapy and ionizing radiation. When further antitumor therapy is not feasible, pharmaco-therapy with combinations of NSAIDs, opioids, and adjuvant analgesics is instituted to raise the pain threshold. Invasive approaches to controlling oncologic pelvic pain are usually considered if dose-limiting side effects arise and cannot be reversed.

Methods of Pain Management in Gyanecological Malignancies
Radiotherapy
Cytostatic therapy
Analgesics - NSAID`s opioids and adjuvant drugs
Epidural / intrathecal narcotics (implantable pumps)
Neurolytic blockade, superior hypogastric plexus block
Intrathecal NEUROLYSIS
Neurosurgical procedures - neurectomies, rhizotomies etc.

Several methods of treatment are available depending upon the origin of pain. It is possible to achieve pain relief by radiotherapy or by cytostatic therapy. Sometimes, anaesthesiological and neurosurgical measures are successful, but the most important method is treatment with analgesics. Strong opioids are given, if pain relief is insufficient under treatment with non-narcotic drugs or weak opioids, like codeine. Morphine and other strong opioids are not reserved for pain control only in terminally sick women, as they can be administered successfully for long periods without severe side effects. If possible, the oral route should be selected. If vomiting occurs, or if patients are unable to take oral medication, morphine can be given peridurally, intrathecally or by infusion. Often, an additional treatment is necessary with different medicaments like tricyclic antidepressants and corticosteroids.

Oral Analgesics used for managing Gynaecological Cancer Pain

Level I (WHO step ladder)
Paracetamol, Piroxicam, Ibuprofen, Ketorolac and Ketoprofen

Level II Tramadol, Codeine Sulphate, Pentazocine, Transdermal Fentanyl Patches

Level III
Morphine oral

Adjuvants Drugs used:
Amitryptiline, Alprazolam, Lorazepam, Fluoxitiene Carpamazepine, Gabapeutin, Diphenyl hydantoin, Corticosteroids.

In pre-terminal and terminal gynaecological patients with persistent cancer pain, now it is possible to carry out some anthalgic methods associated or not to parenteral administration of non-narcotic or narcotic analgesic, i.e. intrathecal neurolytic injections and epidural narcotic administration. Many favourable results have been obtained by means of single or repeated 7% phenol in glycerine injections to patients with advanced but not terminal cancer affected by somatic and segmental pain or by perineal pain. In order to control more extensive pains, epidural injections of morphine in saline have been employed in preterminal patients. This method appears to be the best answer to many problems complained by the patients: pain, depression, malaise. As a matter of fact, low doses of epidural morphine induce both complete pain relief and sedation or slight drowsiness.

1) Neurolytic Blockade
a) Presacral neurectomy and superior hypogastric plexus block. Surgical interruption of the hypogastric plexus (pre-sacral neurectomy) is a well-accepted procedure that has been demonstrated to relieve a variety of painful pelvic conditions, predominantly of nononcologic origin (i.e. dysmenorrhea), as well as pain associated with gynaecological malignancies. Superior hypogastric plexus block, a percutaneous procedure that is analogous to presacral neurectomy, has recently emerged as an important option in the management of intractable pelvic pain of neoplastic origin.

The superior hypogastric plexus (SHGP), also called the presacral nerve, is a retroperitoneal structure located bilaterally at the level of lower third of the fifth lumbar vertebral body and upper third of the first sacral vertebral body at the sacral promontory and near the bifurcation of the common iliac vessels. The SHGP is in continuity with the celiac plexus and lumbar sympathetic chains above. Via the hypogastric nerves, the SHGP innervates the following pelvic viscera: descending colon and rectum, vaginal fundus and bladder, uterus and ovary. In the first published study, SHGP block was shown to reduce pelvic pain by a mean of 70% in patients with cervical cancer.

b) Ganglion impar (ganglion of Walther): This procedure was recently proposed for sympathetically mediated pain involving the perineum and genitals, specially of a burning or urgent nature. The ganglion impar is a solitary retroperitoneal structure located at the level of the sacrococcygeal junction that marks the termination of the paired paravertebral sympathetic chains. Good results and an absence of complications have been reported for perineal pain in patients with cancer of the cervix and cancer of endometrium.

2) Subarachnoid and epidural block
Except in patients with preexisting colostomy and urinary diversions, neuroaxial blocks should be considered only as last resots, and even then great care must be taken to avoid limb paresis. When the above conditions are met, the subarachnoid route may be preferred to epidural administration because with the former, the spread of the neurolytic substance and consequent effect is more predictable. Epidural injection warrants consideration when pain is bilateral; if available, combined unilateral cordotomy with contralateral subarachnoid neurolysis may be considered. Subarachnoid phenol saddleblock is a particularly appropriate option for intractable perineal pain in the present of urinary diversion and colostomy. It is performed with a large bore spinal needle at the L5-S1 interspace with the patient seated and inclined backwards 45o.

3) Intraspinal opioid therapy
Continued administration of opioids intrathecally or epidurally with or without dilute concentration of local anesthetic is an important option for patients with pelvic pain that is refractory to conventional pharmacologic management. Administration can be carried out using a variety of drug-delivery systems ranging from a temporary percutaneous epidural catheter to a totally implanted system. The effectiveness of preimplantation procedure and reversibility of effect makes this an attractive treatment option. Applications for chronic intraspinal opioid therapy are potentially limited, however, by factors that include uneven availability of the technology required for its institution and maintenance, high cost, the development of tolerance, and ineffectiveness in a proportion of patient.

Oral drug therapy through WHO three step ladder is known to relieve cancer pain in 85% of such patients in developing countries. However, oral narcotics reach only 10% of the rural cancer patients in developing countries like India. 80% of patients in India come from rural areas, and many are first diagnosed with cancer when the disease is advanced. Rural patients may ignore early cancer warning signs because of ignorance (illiteracy), fear of painful life threatening disease, social stigma of cancer, long distances, and poverty. Even patients in urban areas receive inadequate pain treatment due to unavailability of narcotics like oral morphine, unfounded fear of addiction, and problems of communication.

NEUROLYTIC TECHNIQUES
Neurolytic blocks are used as an alternative method for relief of pain in terminal cancer patients in developed countries. These have special advantages in developing countries like India. A typical patient coming from a rural area in poor, illiterate or poorly educated, and unfamiliar with western medicine. She cannot afford to go to urban oncology institutes frequently. Due to a shortage of beds in oncology institutes and hospice complexes, we can admit only a few advanced cancer patients to our hospital wards. Treatment aim, therefore, is to control the symptoms, including pain, as quickly as possible. Patients are encouraged to return to their homes in rural areas after control of pain and symptoms is achieved.

Advantages: The neurolytic blocks have the following advantages in home care by relatives of patients particularly in rural area of India:
1. Neurolytic blocks provide longer duration of pain relief.
2. Drugs and inexpensive equipment required are readily available.
Elaborate equipment is not mandatory.
3. Long-term indoor ward treatment is avoided, repeated visits to the
urban pain center are not required.
4. Patient can remain at home pain free even in rural areas where medical help is scarce.

Disadvantages: The neurolytic blocks are known to have the following disadvantages:
1. The blocks are occasionally unpredicatable.
2. Complications like paraesis of muscles are known.
3. Blocks are to be repeated after 6-8 weeks.
4. Elaborate equipment like CT-Scan or C-arm x-ray image intensifier is advocated for accurate placement of the needles.
5. Some patients have to be kept in the hospital for 1-2 days to assess the pain relief and to treat the transitory complications.
Neurolytic blocks are undertaken in advanced cancer patients having severe persistant pain localized within a region or in the limbs. large clinical studies have shown relief of pain in 50-80% patients, particularly with multiple blocks. Significant complications can be reduced to less than 5% by careful selection of patients.
Intrathecal 5% phenol in glycerine for relief of pain cancer of cervix and Uteri
Carcinoma of the cervix is the most common cancer in females in our center (28%). Perineal pain in these patients manifest as a burning sensation, tenesmus and dull aching somatic pain without trigger points.
Vague pain over abdomen with backache signifies relapse of disease in these cases due to resistance to radiation.
We have achieved good results with classic Meher`s technique which consists of performing subarachnoid infiltration with hyperbaric 5% phenol in glycerine at the level of the L5-S1 interspace or higher. Out of 180 patients with perineal pain due to gynecologic malignancy treated with one or more 5% phenol in glycerine blocks, 80% of patients derived satisfactory to excellent results for 4-6 weeks. Using this technique, we have achieved also satisfactory pain relief for 4-6 weeks in 74% of the patients suffering from advanced cancer of the rectum and external genitalia.

References:
1. WHO draft interim guidelines handbook on relief of cancer pain. WHO Technical Document, 1984 CAN/84.2.
2. V. Ventafridda A, Caraceni L, Savita F Commo. WHO Method for Cancer Pain Relief, Indian J Pain 1987;2:78-81.
3. Hay RC. Subarachnoid alcohol block in the control of intractable pain. Anesth Analg 1962:41:12-16.
4. Bhatia MT. Neurolytic Techniques, proceedings of VIth International Congress of pain clinic, 1994, edited by P. Raj et al; WSPC University of Georgia, pp.547-552.
5. Papo I, Visca A. Phenol Subarchnoid Rhizotomy for treatment of cancer pain. Adv Pain Res Ther 1979;2:339-346