Issues and emerging trends in management of visceral pain

The pain is an unpleasant experience. Although protective, it is usually distressing. Everyone wishes to avoid or eliminate it as far as possible. The classification of pain is mainly nociceptive (i.e. pain arising from the stimulation of nerve cells) and neuropathic (i.e. due to nerve damage). Nociceptive pain is due to damage or injury and is of mild and moderate nature which can be contained with Non-Steroidal Anti-Inflammatory Drugs (NSAIDS). Neuropathic pain is moderate to severe in nature which may or may not have an identifiable cause, and seldom responds to classical NSAIDS. They can be bothersome, debilitating and needing immediate attention.

Among the various kinds of visceral pains, on an average, about 14 to 33 per cent of people in different population studies have experienced Non-cardiac chest pain (NCCP). It may be due to a variety of reasons, such as musculo-skeletal chest pain (pain that affects the muscle, tendons, ligaments and bones, due to the release of H+ ions especially in the heart, stimulating the sensory neurons and causing trauma and sudden jerking movements) accounting for about 20.4 per cent of all cases, followed by costochondritis (a benign, temporary inflammation of the costal cartilage, its symptoms often similar to that of heart attack). Once it has been established that musculo-skeletal pain or costochondritis are not the underlying causes of chest pain, Gastro-esophageal reflux disease (GERD) was the most common contributor to chest pain. GERD is a chronic symptom of mucosal damage caused by stomach acid coming up from the stomach into the esophagus. Not surprisingly, it was observed that, in comparison to patients who suffer from pains associated with cardiac disorders, the patients suffering from NCCP were younger, consumed greater amounts of alcohol and were anxiety prone.

The treatment for non-cardiac chest pain has markedly evolved from the past, with more focus being given to GERD and visceral hypersensitivity. While proton pump inhibitors (PPIs) such Omeprazole continue to be the drug of choicewhich reduce the frequency and severity of pain in the case of GERD associated chest pain, promise has been seen with the anti-reflux and anti-secretory treatment by using histamine-2 receptor antagonists (H2RA)  in about 42 to 52 per cent patients under study. H2RAs are a class of drugs that block the action of histamine, a neurotransmitter, on the parietal cells of the stomach, thereby decreasing acid production and providing relief. Significant improvements were also seen in patients who underwent laparoscopic fundoplication. Fundoplication surgery, involves wrapping the fundus (the upper curve of the stomach) around the esophagus and sewing it into place, making the lower portion of the esophagus pass through a small tunnel of stomach muscle. This strengthens the lower esophageal sphincter and prevents the acid from invading the esophagus and causing damage. About 90 per cent of the patients who underwent this surgery reported relief from chest pain while 50 per cent had a complete system resolution.

Coming to non-GERD related non-cardiac chest pain, visceral hyperalgesia (an abnormal increase in the sensitivity to pain) was observed as the most common cause. Thus, the principle behind its treatment is based on esophageal pain modulation. Drugs having visceral analgesic effect such as tricyclic antidepressants, selective serotonin re-uptake inhibitors (drugs increasing the amount of extracellular serotonin or 5-hydroxytryptamine, which is a neurotransmitter involved in the feeling of wellbeing) and theophylline, have become the backbone of therapy involving increase in the threshold of esophageal pain perception. Clinical trials involving Botox as an endoscopic treatment and hypnotherapy have also been partially successful, while conventional medication involving nitroglycerine, phosphodiesterase type 5 inhibitors and calcium channel blockers continue to be in use.

Gastrointestinal pain
Another type of pain on the rise in India, especially among the youth, is gastrointestinal pain. A variety of conditions such as urinary tract infection, endometriosis (a gynaecological medical condition in which the lining of the uterus/endometrium appear and flourish outside the uterine cavity, most commonly on the membrane lining the abdominal cavity of the peritoneum), pelvic inflammatory disease and gastro-esophageal reflux disorder may contribute towards it. However, the commonest cause of this malady has been identified as Irritable Bowel Syndrome (IBS), a functional disorder characterized by abdominal pain, bloating, cramping and diarrhea during or shortly after a meal. One of the causes of IBS is the hyperactivity of the nerves and muscles of the gut leading to heightened sensitivity.

Octreotide, a synthetic analog of somatostatin (a growth inhibiting hormone which regulates the endocrine system as well as decreases acid secretion in the stomach) has been shown to increasethe rectal and sigmoid colon’s perception of pain. Linaclotide, an experimental peptide agonist of guanylate cyclase enzyme (which causes vasodilation in the body) has also been found to be effective as an intestinal secretagogue in the treatment of abdominal pain associated with IBS. Newer studies are now concentrating on the use of probiotics to change the micro flora of the gut as a part of therapy. Women who have IBS, are also more likely to have chronic pelvic pain, urinary frequency and urinary urgency. Chronic pelvic pain is highly common, affecting about one out of seven women in the USA and about 12 to 20 per cent of women worldwide. It is characterized by an intense pain the lowest part of the abdomen and pelvis lasting for more than 6 months. 25 per cent of women are bedridden due to this pathosis for at least three consecutive days a month. Adhesions (internal scar tissues which develop due to injury or surgery and connect parts of the body which are not normally connected) and endometriosis are the leading causes of chronic pelvic pain. As a part of emerging treatments for chronic pelvic pain, many patients responded to extracorporeal shockwave therapy as well as magnetic stimulation, which reduced pain and improved voiding.

Vulvodynia
Another idiopathic visceral pain syndrome commonly plaguing women world over, is vulvodynia, which is a chronic pain in the area surrounding the vaginal opening (vulva). Vulvodynia is classified into two types -  vulvar vestibular syndrome/provoked vestibulodynia and generalized vulvodynia. Vulvar vestibulitis syndrome is limited to the area surrounding the vagina and occurs due to pressure being applied in that region, either due to sexual intercourse or tampon use or prolonged sitting. On the other hand, In Generalized vulvodynia pain occurs spontaneously and is longer lasting. The symptoms are burning and stinging sensations, rawness and soreness. While standard medications such as tricyclic antidepressants, local anesthetics like lidocaine, nerve blocks and surgery continue to be a part of treatment, newer therapies such as the use of novel bio-adhesive patches loaded with 5-Aminolevulinic acid (used as a photosensitizer here) to administer photodynamic therapy to vulvar regions displaying characteristics of vulvodynia are also on the rise. A significant reduction in overall pain symptoms was seen in many patients who underwent photodynamic therapy.  

Pain in pelvic region
Not just women, but many men as well experience pain in the pelvic region and difficulty in urination. This maybe attributed to chronic pelvic pain syndrome (CPPS) or chronic prostatitis, the cause of which is still relatively unknown. CPPS maybe acute (sudden onset of pain) or chronic (persistent pain). It mostly affects men between the ages of 30 to 50. Chronic prostatitis may occur due to nerve problems affecting the prostate gland or autoimmune disorders or inflammation due to urine being forced backwards up into the prostate during micturition or even due to bacterial infections. The treatment for prostatitis includes antibiotics, alpha blockers which are used to treat prostate enlargement, phyto-therapy involving quercetin (a flavonoid having anti-inflammatory properties) and bee pollen, certain neuroleptics, finasteride (a drug used to treat benign prostatic hyperplasia) and pentosan polysulfate (a drug used to treat interstitial cystitis or painful bladder). There is also a growing emphasis on biomedical therapy and bio-psychological i.e. neuromodulatory, physical and cognitive behaviour therapy in the management of symptoms associated with prostatitis.

Also affecting the male pelvic region is the commonly scrotal/testicular pain which was seen in 15 to19 per cent of men post-vasectomy. While  orchialgia and orchidynia (pain in the testes) may occur at any age it is most commonly seen in men in the age bracket of mid to late thirties. The pain may also be a kind of a referred pain, which means pain being felt in a part of the body other than its actual source, and it may be due to radiculitis (inflammation due to irritation of the nerve roots), neuropathy (dysfunction of one or more peripheral nerves of the genito-femoral or ilioinguinal nerves) or irritation of the genital branch of the genito-femoral nerve by small, indirect inguinal hernia. While nerve blocks have been traditionally used in the treatment; a novel therapy involves the usage of pulsed radio frequency.

Thus, we see that pain is an important protective mechanism which draws our attention to the underlying cause and pathology. In the absence of perception of pain, the pathological condition will continue to progress and this leads to catastrophic consequences. For example, in diabetes mellitus, patients, due to neuropathy (loss of nerve function) fail to sense any pain in the leg or foot even in the presence of an ulcer or a wound, leading to gangrene (presence of dead tissue due to lack of blood supply, called as vascular inadequacy). Once gangrene sets in, the amputation of the leg become inevitable. Therefore, pain serves an important role in the checking of pathological consequences. Sometimes, however, pain becomes an unbearable burden and needs to be alleviated as it can interfere severely with the quality of life. Moreover, it is important to know about the nature of pain, as they are indications to many underlying causes and also to select the best way of treatment.