Tag Archives: anti-inflammatory

Loin Pain Hematuria Syndrome (LPHS)

Loin Pain Hematuria Syndrome (LPHS) is an extremely rare disease, where there is unexplained flank pain and Haematuria. Often misdiagnosed as a hypermobile kidney has the same symptoms. This is poorly understood condition for which specific diagnostic criteria are lacking.

Here are some facts about LPHS:

  • LPHS was first identified in England in 1967 among women who were taking birth control pills.
  • Approximately 90% of the reported cases of LPHS are female.
  • LPHS was first noted in men in the 1980’s.
  • LPHS was first noted in the USA in the 1980’s.
  • The first renal autotransplatation for LPHS was done in 1982.
  • Cases of LPHS have been reported from England, Canada, USA, India, Australia, Ireland, Scotland and Germany.
  • The age range for LPHS is from 6 to 50 years.
  • There are approximately 200 cases of LPHS in the world; no doubt, there are more undocumentated cases.
  • Pain attacks due to LPHS can occur several times per week, every few weeks, or every few months. These pain attacks can last from hours to weeks.

    Here are some guidelines to help you decide if you think you need to investigate this problem with your doctor.

  • The condition is mainly characterized by intractable pain involving the kidney and abdominal areas.
  • Microscopic blood or blatantly obvious amounts of it can be seen in the urine. Clot retention can also occur.
  • It is extremely important that physicians recognize the need for adequate pain medication for this disorder.
  • Forcing fluids by mouth or I.V. are very helpful in decreasing the hematuria and in reducing the risk of clot retention.
  • Be prepared to see several doctors and yield to psychiatric exams before you get a correct diagnosis. This is common with any disease that is not common, such as diabetes. LPHS has only been diagnosed in a few hundred people around the entire world, so this is one disease that is not likely to pop into a physician’s head.

    related articles

    Department of Surgery, Royal Prince Alfred Hospital, Sydney, NSW, Australia. agrs@liver.rpa.cs.nsw.gov.au

    Some patients with the loin pain/hematuria syndrome suffer incapacitating flank pain. No effective therapy has been reported. Uncertainty persists concerning the authenticity of the pain and the role of surgery in treatment.

    Forty-six patients with loin pain/hematuria syndrome and intractable pain were evaluated following treatment either by renal autotransplantation (30 patients, 10 bilaterally) or by renal denervation (20 patients, four bilaterally) over a 13-year period.

    All patients had concomitant renal nerve excision and ligation and capsulotomy. There were 37 (80%) women and nine men aged 18 to 61 years (mean age, 33 years).

    Excretion urography and angiography were normal in all patients. Nineteen of 25 (76%) patients in whom renal autotransplantation was successfully accomplished and who completed a follow-up questionnaire were free of pain, including eight of 10 with bilateral procedures.

    The follow-up periods ranged from 1 to 13 years (mean, 8.4 years). Six patients have been free of pain for 10 to 13 years.

    Of 18 patients treated with renal neurectomy who were available for follow-up examination, 12 (67%) developed recurrent renal pain, including four who had pain relief on the other side following previous renal autotransplantation.

    The follow-up period for these patients ranged from 6 to 9.9 years (mean, 8.0 years). Three of four patients with recurrent renal pain following neurectomy were treated successfully by renal autotransplantation.

    The loin pain/hematuria syndrome is a rare cause of incapacitation, predominantly of relatively young females. The pain of the syndrome is organic.

    Renal autotransplantation achieves pain relief in three quarters of patients, but the procedure is often (30%) required bilaterally and has significant complications.

    Renal neurectomy is followed by an excessive incidence of recurrent renal pain.


    What is Loin Pain Hematuria Syndrome?

    by Marc F. Brazie, MD
    Division of Nephrology
    University of Maryland Medical Center, Baltimore, MD

    What is Loin Pain Hematuria Syndrome (LPHS)?

    LPHS is a rare kidney disorder causing attacks of severe flank pain and blood in the urine.

    Who gets LPHS?

    LPHS was first reported in three patients in 1967 who were found to have recurrent attacks of severe flank pain and blood in the urine (hematuria) in whom no other explanation could be found [2]. Since that time, it has been reported in several hundred people worldwide, although it is likely that there are many more unreported cases. It is more common in women (70% of all cases) [3-5], and has been seen mostly in the United States, Great Britain, Australia, and Canada, suggesting a white predominance. While it can start at almost any age, most patients will first develop symptoms in their 20’s [6].

    How do I know if I have LPHS?

    The predominant features of LPHS are recurrent flank pain and blood in the urine. The pain can occur on only one side or both, and may radiate to the abdomen, groin, or inner thigh. Pain episodes may be associated with low-grade fevers and a burning discomfort with urination. The blood in the urine may be overt (called “macroscopic hematuria”), or only detectible on a urine dipstick test or by examining the urine through a microscope (called “microscopic hematuria”). Up to 47% of patients with LPHS also have a history of kidney stones [7], but stones must be absent during pain episodes for LPHS to be diagnosed.

    What causes LPHS?

    As LPHS is a rare disorder, not much is known about the underlying causes. It is thought that there may be a problem with the glomerular basement membrane (GBM), which is the blood “filter” in the kidney, causing bleeding into the kidney tubules. These tubules can then become blocked by the blood cells, causing swelling and increased pressure in the kidney. This in turn leads to stretching of the outer layer of the kidney, called the “capsule,” and pain. Indeed, studies examining biopsies of patients thought to have LPHS have shown that in over 50% of patients, the GBM is abnormally thick or thin [7].

    What should I do if I think I might have LPHS?

    There are many disorders that can cause flank pain and blood in the urine, and as there is no specific test to confirm LPHS, it is considered a diagnosis of exclusion. It is very important to have a thorough evaluation by a kidney doctor (nephrologist) to be sure there is no other cause for the symptoms. This evaluation may involve laboratory tests, radiology studies, or even a kidney biopsy.

    What can be done for LPHS?

    Again, as LPHS is a rare disorder, it is not clear what the optimal treatment is. What is known is that patients with LPHS tend to have normal kidney function, which does not deteriorate over time. Thus, treatment is aimed at pain control and improvement in quality of life. Multiple therapies have been tried, all with mixed results. These include:
    • Medications such at angiotensin-converting enzyme inhibitors (a family of blood pressure medicines which reduce the pressure in the kidney and have been shown to be of benefit to some patients [8]), non-steroidal anti-inflammatory drugs (such as ibuprofen, naproxen, or ketorolac), and narcotic pain medications.
    • Nerve block procedures to decrease the pain signal from the effected kidney, and
    • Surgery to strip the nerves from the kidney, “autotransplant” the kidney (in which it is removed from its normal position and reinserted in the lower abdomen – this has been shown to relieve pain in up to 70% of patient in some reports [3,4]), or in extreme cases, remove the kidney altogether.

    It is best to discuss all the treatment options with your doctor, and ideally as part of a “multidisciplinary” approach involving primary care doctors, nephrologists, psychiatrists, and chronic pain specialists.


    References
    1. Dube GK, Hamilton SE, Ratner LE, Nasr SH, Radhakrishnan J. Loin pain hematuria syndrome. Kidney Int. 2006; 70: 2152-2155.
    2. Little PJ, Sloper JS, deWardener HE. A syndrome of loin pain and haematuria associated with disease of peripheral renal arteries. Q J Med. 1967; 36: 253-259.
    3. Sheil AG, Chui AK, Verran DJ et al. Evaluation of the loin pain/hematuria syndrome treated by renal autotransplantation or radical renal neurectomy. Am J Kidney Dis. 1998; 32: 215-220.
    4. Chin JL, Kloth D, Paulter SE, Mulligan M. Renal autotransplantation for the loin pain-hematuria syndrome: long-term followup of 26 cases. J Urol. 1998; 160: 1232-1235.
    5. Greenwell TJ, Peters JL, Neild GH, Shah PJ. The outcome of renal denervation for managing loin pain haematuria syndrome. BJU Int. 2004; 93: 818-821.
    6. Weisberg LS, Bloom PB, Simmons RL, Viner ED. Loin pain hematuria syndrome. Am J Nephrol. 1993; 13: 229-237.
    7. Spetie DN, Nadasdy T, Nadasdy G, et al. Proposed pathogenesis of idiopathic loin pain-hematuria syndrome. Am J Kidney Dis. 2006; 47: 419-427.
    8. Hebert LA, Betts JA, Sedmak DD, et al. Loin pain-hematuria syndrome associated with thin glomerular basement membrane disease and hemorrhage into renal tubules. Kidney Int. 1996; 49: 168-173.

  • Non-Surgical Ligament Reconstruction

    Is it impossible to have a healthcare system that is driven by profits to also be focused on inexpensive and permanent solutions?

    When reports on ESPN this week revealed that some US Olympic Ski Team members left the country and went where they could use what is considered ìalternativeî treatments for relief of their injuries and pains, it once again elevated the question of why Medical insurance and workmans comp in the U.S. wonít cover procedures like that.

    In many cases, these treatments prove markedly more effective than traditional therapies. The treatment called prolotherapy, used to strengthen weakened ligaments, is widely accepted and used in other countries with national health care systems, including Canada.
    Prolotherapy has been considered ìinvestigationalî for 70 years by the Medicare board; insurance companies will cover it when Medicare decides to cover it.

    The practice of prolotherapy is used by both medical doctors (MDís) and osteopathic physicians (DOís), such as Dr. Jo Ann Douglas of Colorado Osteopathic & Sports Medicine, to treat several different types of chronic pain. It may be the latest alternative therapy to hit the sports medicine scene.

    Doctors are using the treatment successfully for tennis elbow, Achilles tendonitis, patellar tendonitis, back problems, and other common sports injuries. Prolotherapy is also effective in cases of arthritis, fibromyalgia, whiplash, and chronic pain in the neck, back, shoulder, ankle, and sciatica. It relieves disk problems unresponsive to more conservative treatment.

    According to Dr. Douglas, there are approximately 600 licensed physicians in the U.S. that perform this procedure. ìProlotherapy treats the cause of the problem; that is, instability. We inject a solution into the ligament or tendon where it attaches to the bone, which stimulates the bodyís own healing response by creating blood flow to the area, recruiting immune system cells that clean the area, and construction cells (fibroblasts) that rebuild the tissues.

    ìThis is the exact opposite of the current standard of care, which treats pain and inflammation with anti-inflammatories. Prolotherapy promotes the bodyís inflammatory process so that the body can heal itself. In most cases, commonly prescribed anti-inflammatory medications and drastic measures like surgery or joint replacement may not help, and often hinder or even prevent the healing process.î

    According to Dr. Douglas, ìmany patients do not understand why insurance companies will not reimburse for this technique. In many cases it may save the patient from chronic pain management or surgery, which would save money for insurance companies and Medicare as well as treat the cause of the problem for the patient.î

    The federal government hears issues from large special interest groups loud and clear. The drug companies, surgeons and chiropractors are heard; whereby the 600 doctors who perform prolotherapy are a very small voice in the healthcare system. In fact, they were not heard at all until Olympic Athletes went to Mexico to get prolotherapy.
    Vioxx was covered by insurance, even though it had risks. Surgeons continually change their methods and the new surgery techniques are covered by Medicare and insurances. Secondly, surgeons use cortisone for temporary relief even though cortisone has been proven to cause ligament and tendon deterioration, which may only lead to surgery.
    X-rays and MRIís do not always reveal injuries. The number of qualified doctors specifically trained to administer prolotherapy is growing. There are training programs at medical schools now that teach this technique, including how to properly diagnose these injuries.

    Although medical doctors who do prolotherapy will continue to be few until more evidence accumulates, osteopaths like Dr. Douglas have a long track record with the procedure.

    Each injection treatment varies in cost, ranging from less than $100 for smaller joints to several hundred dollars for larger or more complex joints such as those in the neck and back. Most people need 4-6 treatments ó usually administered in a series of injections three weeks apart ó to stabilize the joint

    WHY ISN’T PROLOTHERAPY COVERED BY MEDICAL INSURERS?
    Modern allopathic medical research demands that therapies be proven by double-blind methods. This means that neither the patient nor the physician know which therapy is used. For medications, the pills can easily be made to look alike, and a sugar pill used as a placebo is presumed to have no therapeutic value.

    For procedures like prolotherapy and most surgeries, there is no adequate placebo. Cortisone cannot be used as a placebo because cortisone can only be injected 3 times a year; typically, prolotherapy requires 4-6 treatments.

    The Medicare board wants more data to show the effectiveness of prolotherapy. Drug companies pay for research when it is profitable. They are unlikely to pay for research on prolotherapy because this would not be a profitable venture. In fact, drug companies and surgeons would profit less if prolotherapy would be more widely used, since fewer people would need pain medication and they could avoid expensive surgeries or complications from surgeries.

    Dr. Douglas can be contacted through her Website (www.mycodo.com) which further explains this procedure.

    Jo Ann Douglas, M.S,D.O.
    Board Certified by the American Osteopathic Board of Neuromusculoskeletal Medicine
    Colorado Osteopathic & Sports Medicine

    Sugar treatments for chronic musculoskeletal pain

    News 10 has an article about Prolotherapy, which is use a dextrose (sugar water) solution, which is injected into the ligament or tendon where it attaches to the bone. This causes a localized inflammation in these weak areas which then increases the blood supply and flow of nutrients and stimulates the tissue to repair itself.

    Part of the theory is the injections cause an inflammation that causes healing, and anti-inflammatory drugs stop healing process.

    They also list this link to Magaziner Center in Cherry Hill, N.J. and a phone number at Information on Prolotherapy Injections for Chronic Pain: (856) 424-8222

    History of Medicare’s Prolotherapy Coverage Policy

    The Coverage Issues Manual (CIM) ’35-13, “Prolotherapy, Joint Sclerotherapy, and Ligamentous Injections with Sclerosing Agents – Not Covered,” states that the medical effectiveness of these therapies has not been verified by scientifically controlled studies, and therefore, cannot be covered by the Social Security Act, ‘1862(a)(1), as a “reasonable and necessary” treatment. This policy of non-coverage along with an erroneous Administrative Law Judge (ALJ) opinion issued in favor of Irwin Abraham, MD, in December 1997, on behalf of a Medicare beneficiary, prompted Dr. Abraham to request a national coverage decision reversing the current policy of non-coverage.

    Prolotherapy was last examined for coverage by the Health Care Financing Administration (HCFA) in September 1992. The request had been generated by a beneficiary claiming a benefit from the prolotherapy treatments she had been receiving. HCFA received a number of anecdotal accounts of significant benefit derived from prolotherapy treatments, but when a literature search was conducted it failed to produce any scientifically sound studies on which to base a coverage decision.

    The ALJ decision in favor of Dr. Abraham was based on Dr. Abraham’s ability to successfully bill HCFA under the CPT code 20550, “Injection, tendon sheath, ligament, trigger points or ganglion cyst” in the past. However, after the carrier identified the treatment of Dr. Abraham’s patient as prolotherapy, the carrier denied further payment. The ALJ reasoned that because the treatment had been paid for in the past, the carrier was estopped from further payment for the same procedure on the same patient who claims a benefit from the treatment. The ALJ further reasoned that payment for this treatment in the past and the teaching of this method in some medical schools is sufficient evidence that HCFA had modified its policy regarding prolotherapy. Unfortunately, the ALJ did not address the possibility that the carrier had mistakenly paid for the treatment before recognizing it as the non-covered prolotherapy. Furthermore, because the carrier failed to submit evidence that prolotherapy was indeed experimental and investigational, the ALJ determined that without advance notice to the beneficiary that the procedure was non-covered, Medicare would cover the treatment as reasonable and necessary.



    HCFA conducted a new electronic literature search using MEDLINE and Ovid. The results only provided editorial articles devoid of any new scientific research. Also, HCFA staff searched the internet and contacted the American Association of Osteopaths for a complete list of current scientific evidence on the efficacy of prolotherapy. None of these efforts produced significant evidence to support the coverage request.

    Analysis of Scientific Evidence

    In light of the aforementioned ALJ decision, Dr. Abraham’s confusion regarding the policy here is just; however, an ALJ decision is neither binding nor precedent setting on HCFA’s national coverage decisions. Dr. Abraham supplied HCFA with five articles, two of which are clinical trials that support his request for coverage of prolotherapy. Neither of these articles contain sufficient evidence to persuade HCFA to alter the policy now in place.



    The Ongley et al. article: “A New approach to the Treatment of Chronic Low Back Pain,” published in The Lancet, July 1987, studied 81 patients with chronic low back pain with an average duration of ten years in a double-blinded study to compare prolotherapy injections with a non-proliferant injectable course of therapy. Forty of the 81 patients received a regimen of forceful spinal manipulation and injections of a dextrose-glycerine-phenol solution. The 41 patients in the placebo group received less extensive initial local anesthesia (<10 ml 0.5% lignocaine compared with infiltration of 60 ml 0.5% lignocaine in treatment group), a non-forceful manipulation and saline as a substitute for the proliferant used in the experimental group. Also, the experimental group on the first day received a regimen including infiltration of triamcinolone (an anti-inflammatory) into the gluteus medius origin, whereas the placebo group only received lignocaine into the gluteus medius origin. The program included exercises in both groups to encourage the synthesis of the new cells with existing connective tissue. While the authors concluded that "the experimental regimen is a safe and effective treatment for chronic low back pain that has not responded to other conservative forms of treatment," they write earlier in the body of the results section of the paper that "(i)ndependent evaluation of physical signs revealed no significant differences between the groups after treatment."


    The Ongley study fails to support the coverage of prolotherapy for a number of reasons. The authors report a subjective improvement in pain amelioration, but they fail to supply any persuasive objective criteria on which to base a coverage decision that must be grounded in scientifically valid evidence. Even the authors acknowledge in their conclusion “(f)uture studies may be needed to analyse [sic] the relative import of each component of the overall procedure.” Since the authors chose to provide the participants with manipulation, exercises and anesthesia in addition to the proliferant and saline injections, it is difficult, if not impossible, to isolate the component of the treatment which gave the participants the reported relief.




    Establishing a link between the subjective improvement in pain management and a particular regimen is problematical because the participants in the experimental group received a different preparation course with more anesthesia and a forceful manipulation as opposed to the placebo group’s faux manipulation. Since the study did not treat the proliferant injections as a single variable, there is no way to positively identify prolotherapy as the cause of the pain relief rather than the forceful manipulation. Also, because Medicare currently covers forceful manipulation and massage therapy by a qualified provider, HCFA would need evidence that the addition of another variable, such as prolotherapy, to a patient’s course of treatment would provide greater benefit than that which is currently covered. Furthermore, even if the results concluded that the benefit in pain reduction could be positively attributed to prolotherapy, the sample size of 81 patients is really an insufficient number on which to base a positive national coverage decision.




    The more recent study submitted by Dr. Abraham also falls short of the requisite level of evidence needed for a national coverage decision. The Klein et al. study, “A Randomized Double-Blind Trial of Dextrose-Glycerine-Phenol Injections for Chronic, Low Back Pain” published in 1993, fails in much the same way as the Ongley study before it. Again, the number of participants is small; therefore it would be difficult to use the results in support of a newly crafted national coverage decision.

    The Klein study was comprised of 79 patients, 39 of which were placed in the proliferant group. Thirty of 39 patients in the proliferant group achieved a 50% or greater diminution in subjective pain or disability. The control group was not a true placebo because “the patients received four of the five active interventions of the full treatment regimen and demonstrated statistically significant within-group improvements compared to baseline disability and pain scores.” Twenty-one of 40 patients in the placebo group reported a 50% or greater diminution in subjective pain and disability scores. A response of more than 50% of patients in the control group reporting improvement suggests that an actual treatment effect rather than a pure placebo response occurred. Even the authors note, “(t)he interventions shared by both treatment groups, including exercises, injection of local anesthetics, repeated needling, and manipulation may all enhance the success of the procedure, but the relative contribution of each intervention requires further study.”

    The authors identify that further studies are needed to show greater improvement in treating pain with prolotherapy because “the statistical significance was only borderline” when the experimental group was compared to the control group. Also, “objective testing of range of motion, isometric strength, and velocity of movement showed significant improvements in both groups following treatment, but did not favor either” the proliferant or the control group. Further, “the MRI and CT scans showed significant abnormalities in both groups, but these did not correlate with subjective complaints and were not predictive of response to treatment.”

    A total of 160 patients studied over the past twelve years, with only 79 of the patients receiving the proposed treatment, is not a large enough sample to support a change in the coverage policy. More studies with larger control and experimental groups must be evaluated using regimens designed to isolate variables and correlate them to positive results. Ideally, these studies would consist of improvements in both objective and subjective measurement tools. However, substantial and statistically significant improvements in subjective pain scores could be persuasive if HCFA could attribute the patient benefit to the prolotherapy regimen.

    ClinicalTrials.gov shows an closed study “Joint Injections for Osteoarthritic Knee Pain” to determine whether prolotherapy can decrease pain and disability from knee osteoarthritis.

    Medications

    ANALGESICS.

    i) Non-steroidal anti-inflammatory drugs (NSAIDs) have been used for 150 years in Europe, and probably for a great deal longer in the East, in the form of willow bark extract. Useful when given appropriately, examination of the chronic pain population indicates that a very high number of patients are intolerant to these drugs because of gastrointestinal or other side-effects. There are two possible hypotheses for this. Firstly, chronic pain sufferers tend to be somewhat hypochondriacal and intolerant of body symptoms in general and thus less tolerant of real or perceived side-effects when taking medication. The second is that there may be a sub-group of patients whose pain is not managed well early on. NSAIDs may produce side-effects, limiting their use. With no pain relief, the patient fails to exercise. This hampering of their rehabilitation because of inadequate analgesia may contribute significantly towards the chronicity.

    Recently COX2 antagonists have come on the scene, but the first wave of these have been disappointing in the UK, in that the side-effect profile does not appear to be particularly better than the present drugs (Meloxicam, Etodolac). The newer drugs, Vioxx and Celebrex, are now available in the USA and will soon become available in Europe. Their arrival is awaited with eager anticipation, but the results may prove to be disappointing. The products may not be as side-effect free as they first seem.

    ii) The use of opioid drugs for the management of chronic non-malignant pain is fraught with difficulties, some real and some perceived. Morphine itself has tended not to be prescribed for chronic pain, because of a fear or stigma concerning Morphine. Physicians may fear dependence, tolerance and side-effects. There is a wide difference of opinion, which is still to be resolved; however, some patients can have their pain adequately controlled with opioids, without an unacceptable level of addiction problems. The potential risk of addiction remains a very real problem for a minority. Also, a significant number of patients with chronic pain complain of bothersome side-effects from medication. Mobility and distress must be monitored and benefits must accrue in both these parameters, as well as in reduction of pain.

    iii) In the UK and in the USA, traditionally most patients with chronic pain receive an opioid derivative such as Codeine, Dihydrocodeine or Dextropropoxyphene. In the past Pentazocine and Buprenorphine enjoyed a passing vogue but are now little used. Pentazocine proved to have unacceptable side-effects, and Buprenorphine, originally thought to be non-addictive, was shown to have addictive potential and since being classified as a controlled drug has enjoyed little popularity. Nefopam has limited efficacy and popularity, and Meptazinol is short-acting, and often associated with an unacceptable level of side-effects.

    Recent work suggests that Codeine and Dihydrocodeine are merely pro drugs for Morphine, and exert their action through metabolism to this compound. Given that a significant number of the population do not have the metabolic pathway to facilitate this, it is not surprising that there is a significant failure rate to produce any analgesia at all and that patients getting analgesia seem to get limited relief-hence possibly the popularity of these preparations being compounded with Paracetamol. There is good evidence that in some patients, much of the analgesic effect in these combined preparations lies with the Paracetamol itself, whilst many of the side-effects lie with the opioid.

    v) Tramadol hydrochloride is an orally active, clinically effective, centrally-acting analgesic. It can produce analgesia that has been compared to Codeine or Dextropropoxyphene. It has been used in post-surgical pain, obstetric pain, cancer pain and chronic pain of mechanical and neurogenic origin. Analgesic tolerance is not a significant problem, and psychological dependence and euphoric effects are minimal. There are a significant number of patients in the chronic group who develop side-effects, but many of those who tolerate the drug get useful benefit in pain reduction. This slow-release formulation is an appropriate vehicle for chronic pain management.

    Tramadol has an affinity, albeit relatively weak, for mu opioid receptors. It is also a neuronal uptake inhibitor. The monoamine neurotransmitters 5HT (Serotonin) and Noradrenaline (NA) are involved in the inhibition of spinal cord dorsal horn neurone responses to painful stimulation (i.e. closing the gate). Analgesia can result from activating the pain inhibitory pathways originating from higher CNS levels, and containing these neurotransmitters. Tramadol inhibits the uptake of 5HT and Noradrenaline but not Adenosine, Cyclic AMP, Dopamine, or Gaba.

    Metanalysis by Moore and McQuay indicates an appropriate dose response curve for Tramadol, and suggests a reduced number needed to treat to show therapeutic efficacy as compared with Codeine, in doses of 75 to 150 mg. Nausea, vomiting and dizziness are greater than with Codeine, somnolence about the same and constipation much less. In the chronic pain situation nausea and vomiting are attenuated with usage, as is somnolence for both drugs, but constipation remains a particular problem with Codeine and Dihydrocodeine, and less of a problem with Tramadol.

    Side-effects from Tramadol can be minimised by starting with a low dose and increasing gradually. There is evidence that this reduces the side-effects and improves tolerance. According to need, it can be started in a low dose of 50 mg daily or twice a day, and gradually titrated to reach 50 mg three times a day by day 3. Once a patient is established on a therapeutic dose, they can be put on the slow-release formulation to provide round-the-clock analgesia.

    B. PSYCHOACTIVE DRUGS.

    i) Anticonvulsants are well acknowledged as being effective in the management of shooting pain, for example: trigeminal neuralgia and the shooting element of neurogenic pain, such as post-herpetic neuralgia, diabetic neuropathy and similar conditions. Carbamazepine appears to be the most effective drug although there is a higher incidence of side-effects than with Sodium Valproate. Recently Gabapentin and Lamotrigine are enjoying popularity, either as “add on” drugs, or as sole agents. Further drug development of these types of agents might produce useful efficacy in the future.

    ii) Tricyclic antidepressants are one of the most commonly used analgesics in pain clinics. This is not for the specific antidepressant action, but is more associated with the activation of pain inhibitory pathways. This appears to be less of a feature with the tetracyclic agents, and has meant that their usage in chronic pain has as yet remained unproven. This is of course is disappointing as the side-effect profile is significantly better. The sedative effect of Amitriptyline can be harnessed to good usage by giving the tablet one or two hours before retiring, and it should not be used during the day.

    ANALGESIC PAIN MANAGEMENT

    In general, patients with pain can be given a trial of Paracetamol. An appropriate non-steroidal can be used if there is an inflammatory process, and continued if these are effective and if side-effects are minimal. The next optimal step in the analgesic ladder will be the use of agents like Tramadol, Dextropropoxyphene, or Dihydrocodeine, with long-acting preparations being ideal for chronic pain. At present, slow-release Tramadol would appear to be the most effective drug in chronic pain for this group of patients. If side-effects preclude its usage, one of the other agents can be considered.

    Finally a small group of patients might be suitable for the use of opioids themselves.

    In conjunction with this ladder, anticonvulsants and tricyclic antidepressants can be considered, for their specific and appropriate actions on shooting and burning pain, usually of neurogenic origin.