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Normally when the cells grow old or get damaged, they die, and new cells take their place. Sometimes, this process goes awry. New cells form when the body doesn’t need them, and old or damaged cells don’t die as they should. This accumulation of extra cells form a mass of tissue called tumor or cancer. Cancer is the condition when cells in the body divide and grow uncontrollably and start spreading and infiltrating to other parts of the body. Cancer is the uncontrolled growth of abnormal cells anywhere in a body. These abnormal cells are called cancer cells, malignant cells, or tumor cells.
Many cancers are identified by the name of the tissue that the abnormal cells originated from, e.g. breast cancer, lung cancer, colon cancer, mouth cancer, brain cancer, skin cancer etc. The majority of cancer patients experience pain at some time or another. The pain results from the cancer itself or from its treatment. In some cases, people who have been cured of their cancer also continue to suffer from pain. Pain or discomfort from the cancer and its treatment can be controlled most of the time. There are various medicines and methods available to alleviate cancer pain. People having cancer along with pain need to inform their doctor immediately. The earlier the pain treatment is started, the more effective it is. Cancer pain is caused due to many reasons but most cancer pain occurs when a tumor presses on nerves or body organs or when cancer cells invade bones or body organs. Cancer treatments such as chemotherapy, radiation, or surgery also may cause pain.The symptoms of cancer pain differ from person to person. Pain and other symptoms depend on the type of cancer, the stage of cancer, the extent of the cancer and the patient’s pain threshold (tolerance for pain). Cancer pain can range anywhere from mild to severe and occasional to constant.
Pathophysiology of Cancer Pain
The pathophysiology of cancer pain is complex. It involves inflammatory, neuropathic, ischemic and compression mechanisms at multiple sites. Knowledge of these mechanisms and the ability to decide whether a pain is nociceptive, neuropathic, and visceral or a combination of all three will lead to better pain management. Cancer pain has the same neuro-patho-physiological pathways as non-cancer pain. Cancer pain is a mixed mechanism pain. It rarely presents as a pure neuropathic, visceral or somatic pain syndrome. It involves inflammatory, neuropathic, ischemic and compressive mechanisms at multiple sites. Development of pain over time is complex and varied. It depends on the cancer type, its treatment and underlying concurrent morbidities. Opioids are the mainstay of treatment and are associated with tolerance. A variety of neurotransmitters modulate pain sensations at the level of the synapses. Some of the neurotransmitters are serotonin, noradrenalin, prostaglandins, substance P, endorphins, and enkephalins. These neurotransmitters are active at the level of the nociceptors and at the level of the spinal cord and the brain. Nociceptive pain is due to stimulation of normal pain receptors (nociceptors) in the peripheral nervous system that detect tissue damage from mechanical (pressure or stretch), chemical, and thermal stimuli. Local inflammation causes nociceptive pain through the release of prostaglandins, substance P, serotonin, histamine, acetylcholine, and bradykinin. Neuropathic pain results from pathophysiological changes to the peripheral or central nervous system. The changes to the peripheral nervous system can be caused by trauma, distortion, cancer treatment (chemotherapy or radiation therapy), attempts of the nervous system to respond or regrow after damage, or even unrelieved pain. Central nervous system changes include sensitization, and central pain syndromes. The cause of neuropathic pain may be difficult to identify when compared to nociceptive pain.
Classification And Types of Cancer Pain
1. Acute and Chronic Cancer Pain: Cancer pain may be acute or chronic depending on its duration. Acute cancer pain lasts for less than 6 months. Chronic cancer pain is continuous pain, lasting more than 6 months. Cancer pain may be an early or late symptom. Bone cancers or testicular cancer are predominantly presented with early pain. Persistent and continuous headache not responding to analgesics could be a sign of brain tumor or brain metastasis. Back pain can be a symptom of cancer of the colon, rectum, or ovary with or without metastasis of vertebrae. Cancer patients with rapid growing malignant cancer may not survive for more than 6 months. Aggressive rapid growing cancer causes severe and intolerable pain during last few weeks. Cancer is the second most common cause of death after heart disease. Cancer can be cured in few cases depending on early diagnosis and aggressive treatment. Non-aggressive cancer can give a lifetime of over 5 years in some cases after extensive therapy. Advanced aggressive cancer associated with metastasis is fatal and gives limited time. The life span can be prolonged for weeks to months after cancer treatment. Periodic check up of urine, blood, sputum and stool can be helpful in early diagnosis. Cancer is either benign or malignant.
2. Benign Cancers: In this type of cancer, the tissue or cells enlarges in size, but do not infiltrate into the surrounding tissue. Metastasis or spread to other organs through blood or lymphatics is not commonly observed with benign cancer. In few cases, benign tumor size could be massive and may cause erosion of surrounding normal tissue secondary to pressure and ischemia. Ischemia is diminished or lack of blood supply to normal tissue. These changes occur secondary to pressure and compression of blood vessels. Ischemic tissue may end up necrotic and lead to symptoms such as nausea, vomiting, dizziness and bleeding. Some time massive size of tumor can cause obstruction of organs followed by constipation and retention of urine or stool.
3. Malignant Cancers: This type of cancer spreads to surrounding and distant tissues, as well as organs. Local cancer tissue spread involves increase of size as well as penetration and infiltration of surrounding normal tissue or organs. Distant spread is metastasis and observed with spread of cancer cells into distant organs through blood or lymphatics. Penetration of cancer tissue into blood vessel causes ischemia by obstruction to flow and bleeding by tear or rupture of blood vessels. Tear or rupture follows life threatening major or minor bleeding. Cancer tissue may spread to liver, brain and lungs through blood vessels and lymphatics. Tumor tissue mass is called metastasis when spread into other distant organs.
Epidemiology of Cancer Pain
Pain may not be the first symptom in diagnosis of cancer. In various studies of different cancer patients, between 19 to 49% of patients had pain as early symptoms. Pain could be a predominant symptom in metastatic cancer than benign cancer. Cancer could be diagnosed earlier if other symptoms with or without pain are closely monitored. Pain symptom when occurs in over 60% patients, the cancer may have progressed beyond primary location.
Epidemiologic Studies Have Revealed Following Incidence And Prevalence Of Cancer Pain:
- Chronic cancer pain is observed in 30% of all cancer patients.
- Chronic cancer pain is as high as 90% in advanced cancer patients.
- Chronic pain is under treated in over 50% of patients.
- Most common cause of pain in 60 to 80% cancer patient is bone metastasis, tumor infiltration and pressure over nerve or pain receptors. The most common cancer pain is from tumors that metastasize to the bone.
- Chemotherapy, radiation and post surgical pain are observed in advanced cancer patients.
Economic Consequences of Cancer Pain Are As Follows:
- Lost income.
- Enormous cost to patient as out of pocket expense and health care.
- Lost productivity at work.
- Annual expenses for treatment and lost income are close to 200 billion dollars a year.
- Impaired daily living.
Causes And Risk Factors for Cancer Pain
Causes of cancer pain are many, but most cancer pain occurs when a tumor presses on nerves or body organs or when cancer cells invade bones or body organs. Cancer treatments such as chemotherapy, radiation, or surgery also may cause pain.
The Following Are The Causes For Cancer:
- Chemical or Toxic Compound Exposures: Benzene, asbestos, nickel, cadmium, vinyl chloride, benzidine, N-nitrosamines, tobacco or cigarette smoke (contains at least 66 known potential carcinogenic chemicals and toxins), and aflatoxin.
- Ionizing Radiation: Uranium, radon, ultraviolet rays from sunlight, radiation from alpha, beta, gamma, and X-ray-emitting sources.
- Pathogens : Human papillomavirus (HPV), EBV or Epstein-Barr virus, hepatitis viruses B and C, Kaposi’s sarcoma-associated herpesvirus (KSHV), Merkel cell polyomavirus, Schistosoma spp., and Helicobacter pylori; other bacteria are being researched as possible agents.
- Hereditary: A number of specific cancers have been shown linked to human genes. E.g. Breast cancer, ovarian cancer, colorectal cancer, prostate cancer, skin cancer and melanoma.
Causes of Chronic Intractable Cancer Pain
- Infiltration of cancer cells into normal soft tissues and bones.
- Pressure or invasion on surrounding sympathetic and somatic pain nerves.
- Side effects from chemotherapy such as peripheral neuropathy.
- Radiation therapy causes inflammation, tissue necrosis, tissue injuries and scarring. Inflamed tissue heals with scarring. Scar tissue may encroach upon the nerve causing severe pain.
- Ischemic pain secondary to obstruction of blood vessels causing poor circulation.
- Bone fracture and metastasis.
Most of the pain in cancer patients is because of tumor mass pressing on soft tissue, bones or nerves. Pain intensity depends on direct contact with nerve and nerve receptors. Advanced cancer is extremely painful because the cancer tissue encroaches and penetrates normal organs, nerves and nervous system. In few cases chronic pain is excruciating secondary to cancer tissue infiltration into spinal cord.
Cancer Pain Following Spinal Cord Compression: Three layers of membrane called dura, arachnoid and pia surround spinal cord. Dura is the outer layer and pia is the inner layer. Pia membrane is closely attached to spinal cord. Cerebrospinal fluid (CSF) consists of water, element of glucose and electrolytes. CSF lies between pia and arachnoid membrane, also known as subarachnoid space. CSF and three layers of membrane (pia, arachnoid and dura) surround and protect spinal cord from injuries. Nerves come out of spinal canal from right and left side through transverse foramina. Primary or metastatic cancer cells can spread into spinal canal through transverse foramina. Alternatively malignant cancer tissue may spread into spinal canal either by triggering bony metastasis of vertebral body or by the developing growth within the spinal canal. Metastasis of spinal cord occurs through spread by lymphatics and/or blood. Most common cause of spinal cord compression is metastatic tumor mass of vertebral body overrunning the anterior half of spinal cord. It may also spread through supplementary bones of vertebrae into spinal canal and spinal cord. Spinal cord spread causes compression of spinal cord and nerves.
Dermatome Spread of Symptoms: This depends on the segment of spinal cord compressed by primary or metastatic tumor. Cervical spread may cause symptoms in neck, upper extremities or level below the tumor encroachment of spinal cord. In cervical spinal cord compression, symptoms such as numbness and weakness may be wide spread causing monoplegia involving only one limb or paraplegia involving both limbs of upper or lower extremities or in few cases quadriplegia. Intensity of pain increases with certain commotions such as coughing or sneezing. These physiological disturbances cause pressure changes in spinal canal. Activities or movement of vertebral column such as flexion, extension or lateral rotation can also trigger severe intractable pain. Continuous pressure on sensory and motor nerve ultimately results in permanent nerve damage. Permanent destruction of nerves to bladder and intestine initiates loss of control on bladder (bladder incontinence and retentions) or bowel function (bowel incontinence and retentions).
Bone Pain Related to Cancer: Cancer tissue may spread into skeletal system, either distant skeleton by metastasis or confined at the primary cancer site. Example: Lung cancer in advanced stage may spread locally into ribs or to distant skeletal system such as extremities into femur and humerus bone. Pancreatic and abdominal cancer can spread to vertebrae. Cancer that has spread into bones causes osseous pain and also occasional fracture. Fracture of bones itself can cause severe pain.
Surgical Pain Related to Cancer Treatment: Surgical treatment of cancer may include excision of tumor mass and/or excision of metastasis tissue. Surgery could be biopsy or extensive operation causing substantial tissue trauma involving several dermatome segments of spinal cord. Surgery pain is acute and nociceptive. Cancer pain is chronic and neuropathic. Pain felt by patient is enormous and diverse than cancer pain, but severity may be considerably complex and intractable. Resistance and tolerance to pain medication may set a challenge to treat post-surgical pain. Sometimes stubborn resident physician or attending physician may not request assistance from pain specialist. Most of the surgeons will consider the same modalities of analgesics for cancer and non-cancer patients following surgery. Procedures related to cancer pain, such as biopsies, blood draws, lumbar punctures, laser treatments etc. can cause pain.
Phantom Pain: Phantom pain is a neuropathic pain caused by excision of the nerve. It is commonly observed in an amputated limb and mastectomy. Phantom pain is difficult to treat. Phantom pain results in neuropathic complex regional pain syndrome.
Severe Cancer Pain Causes Cognitive Symptoms As The Following:
- Severe cancer pain is also observed after chemotherapy.
- Chemotherapy complication causing increase in pain
- Mouth sores (mucositis).
- Peripheral neuropathy (numb and painful sensations in the feet, legs, fingers, hands and arms).
- Constipation, diarrhea, nausea, vomiting and abdominal cramps.
- Some people also experience bone and joint pain.
- Risk of infection after chemotherapy increases as immunity is compromised in pain and infection.
Signs and Symptoms of Cancer Pain
Cancer can develop in any organ and tissue. The characteristics and influence of symptoms depends on location and size of cancer. Symptoms could be common symptoms, specific warning symptoms and/or deceptive non-specific symptoms.
- Common symptoms may not suggest any particular organ system or region of the body involvement.
- Warning symptoms could be early and specific. Warning symptoms may assist in early diagnosis of cancer.
- Deceptive symptoms could be secondary to underlying disease or cancer. If symptoms are secondary to disease and not cancer then it may lead to unnecessary investigation and treatment.
- Common symptoms: Fatigue, pain, loss of weight, fever, night sweating, persistent coughing, urinary retention and constipation.
Specific Warning Symptoms: These are more diagnostic oriented.
- Pain, weight loss, night sweating and fever: all types of cancer can cause these symptoms.
- Blood in saliva: Caused by cancer of oral cavity, tonsil, pharynx and larynx.
- Hoarseness: Caused by cervical lymph node, cancer of larynx.
- Non healing ulcer and /or white or red patch in oral cavity: Caused by cancer of tonsil, tongue and gum.
- Repeated infections such as bronchitis, sinusitis: Caused by cancer of lungs, trachea and bronchi.
- Persistent cough, blood in mucus: Caused by cancer of lungs, trachea and bronchi.
- Constipation and/or Obstruction: Large Intestine, rectum cancer.
- Continuous diarrhea, pencil thin stools: Colon cancer.
- Multiple bowel movements with no stool: Cancer of small intestine.
- Blood in stool, Anemia: Cancer of small or large intestine.
- Anal itching, pain: Anal or rectal cancer.
- Anemia and Flank pain: Cancer of Kidney.
- Abnormal discharge, breast lump: Breast cancer.
- Swelling and painless mass over testicles: Cancer of Testicles.
- Male urinary infection, enlargement prostate : Cancer of Prostate
- Pelvic pain : Ovarian cancer.
- Blood in urine, frequency, pressure feeling, urinary infection: Cancer of Urinary Bladder.
- Heartburn, Barrett esophagus, difficulty swallowing : Cancer of Esophagus
- Vaginal bleeding, discharge, postmenopausal bleeding : Cancer of uterus
- Itching, skin discoloration, infection like psoriasis, non healing sores: Skin cancer.
- Moles- multicolored, irregular edges, bleeding, larger moles: Melanoma.
- Deceptive and misleading symptoms: May or may not be associated with cancer.
- Regurgitation, epigastric pain: Esophageal ulcer or varices.
- Hemorrhoid, diarrhea, fissure : Rectal bleeding
- Gastric or stomach pain : Gastric Ulcer
- Anemia : Iron deficiency.
- Varicocele, epididymitis: Testicle vascular disease or infection.
- Urinary infection: Bladder stone.
- Vocal cord polyp: Larynx.
- Wart mole: Skin Cancer.
- Ulcer, psoriasis: Skin.
Cognitive symptoms observed in chronic cancer pain are: Depression, fatigue, tiredness, anxiety, anger, irritation, loneliness and isolated feelings, apprehension, fear, memory lapse, and attention deficit.
Cancer Pain Symptoms Secondary To Spinal Cord Compression Are:
- Initial mild to moderate pain followed by severe to very severe pain in very short period of time.
- Numbness and weakness in extremities with compression of sensory and motor nerves.
Evaluation of Cancer Pain
- Detailed Comprehensive History of Cancer Pain: Detailed history of cancer pain provides valuable information to consider appropriate treatment. History should be accurate and comprehensive. Patient or intimate relatives may be writing diary of complaints, which may include history of pain. Description of pain such as dull, aching, throbbing, stabbing, piercing, pinching, sharp, aching, burning and tingling suggests evidence of nociceptive or neuropathic pain. Patient may add descriptive words such as “worst possible pain experienced in my life” suggesting pain is intractable and severe. Location of pain such as headache, neck pain, throat pain, and chest pain, abdominal pain, back pain or pain over upper or lower extremities suggest the source of pain.
- Intensity of Cancer Pain is expressed as mild, moderate, severe or very severe, also described as Visual Analogue Score (VAS) from 0 to 10. Zero is no pain and 10 is worst possible pain. Duration of pain may be described as days, weeks, months or years. Pain interval may be continuous or intermittent. Pain may be continuous with moderate intensity and intermittently severe to very severe of VAS score 10. Cancer patient may or may not suffer with continuous pain, but intermittent dull to extremely severe pain. History of intermittent pain may include how often pain comes and how long does it last. When pain comes, is it always mild, moderate or severe? If pain is sudden in occurrence, how long pain lasts. In 24 hours how many incidents of pain are observed.
- Initial Phase: Cancer patient in initial phase may control pain by maintaining inactivity or trying medication sold over the counter. If medications are taken then the pharmacological name, dosage and how often the medication is consumed is important history to evaluate pain and suffering as well as response to treatment. Some cancer patients may have been trying herbs or homeopathic medications. History of any side effects to medication is also important. History will include any medications taken in the past for any other illnesses and leading side effects.
- Patient Activities: Detailed history of patient’s activities should be documented. Activities limited by pain and activities improved after pain medications should be recorded. Patient’s quality of life is defined by the activities.
Changes In Vital Signs Following Severe Intractable Cancer Pain Are :
- Tachycardia: Increase in heart rate
- Hypertension: Increase in blood pressure
- Rapid breathing
These signs are observed mostly in few patients with inadequate pain relief. Adequate treatment of chronic cancer pain will eliminate some of these symptoms.
Treatment for Cancer Pain
Cancer Pain Treatment Includes
- Radiation therapy.
- Treatment of symptoms other than pain.
- Treatment of Pain.
Treatment of Chronic Cancer Pain
Early cancer pain is mild to moderate and later it may become intractable and severe. Treatment of mild to moderate pain:
- NSAIDs: Naproxene, Advil.
- Adjuvant pain medications like Cymbalta (antidepressants) and Neurontin (antiepileptic).
Treatment of Severe Intractable Cancer Pain
- Opioids, if not responding to NSAIDS.
- Adjuvant pain medications like Cymbalta (antidepressants) and Neurontin (antiepileptic).
- Interventional Pain Therapy: Nerve block, Nerve ablation using radiofrequency and cryotherapy.
- Spinal cord stimulator
- Programmable pump delivering intrathecal medications.
Treatment Of Cognitive Symptoms Associated With Chronic Cancer Pain
- Depression – antidepressants.
- Anxiety – Anti-anxiety or anxiolytic medications.
Difficulties In Treating Chronic Cancer Pain
- Resistance to pain medication
- Emotional suffering
- Denial of end result of cancer treatment
- Secondary gain
- Apprehensive family
Alternative Treatment for Cancer Pain
- Psychotherapy for denial
- Family discussion
- Social and spiritual communication
Cancer Pain Management And Informed Consent
- Informed Consent:Treatment of cancer patients involves patient and patient’s families. Families could be spouse, children, parents and close relatives. Patient’s pain is somatic pain secondary to cancer. Family members or group of family members suffer with emotional pain. Emotional pain becomes predominant when spouse, children, parents and family members are very close to patient. Pain medications such as opioids causes unwanted side effects such as drowsiness, sleepiness, nausea, vomiting, constipation and loss of appetite. These symptoms can bring apprehension within family members leading to multiple questions.
- Registered nurse as a pain coordinator can answer most of the questions. Pain coordinator has an important role in explaining the change of treatment if needed or observation of any complications. Pain coordinator would be available on short notice, as physician may be tied up in other more urgent schedules. Informed consent is an important part of the treatment, as it brings all the parties together before initiating the treatment and also during continuation of the treatment if change is needed in medication or dosage.
- Audio or visual and/or written information of pain therapy and choices should be available for patients. Patients will work with their doctors once detailed information of pain therapies and choices are read by the patients and their close relatives. The doctor should not insist on treatment which the patient has rejected. Patient should not be convinced to accept the treatment, which could be harmful or riskier than the possible benefits. Some, especially exhausted, terminally ill patients, may not wish to be involved in making pain management decisions. Patient may delegate such choices to their physicians or legal guardian. The patient’s participation in ongoing treatment is essential, but could be counterproductive if patient is confused and disoriented. Patient’s choice to have minimum pain relief must be respected. Achieving adequate control of pain with minimum side effects is sometimes difficult. Side effects end up with poor quality of life, exhaustion, lethargy, somnolence and drowsiness. In spite of inadequate pain relief and several side effects, often oral, intramuscular or intravenous opioid treatment is continued for chronic cancer pain instead of intrathecal route of opioid treatment. Although cancer pain can be relieved, surveys have shown that pain is often undertreated in many patients. Patients may be reluctant to report their pain to avoid opioids; patients may be reluctant to use morphine and other opioids for pain control because of fear of addiction. Addiction is extremely rare in people with cancer.
Informed Consent Is Advised For:
- Initiating medications.
- Change of medications or introduction of new medications.
- Consulting a specialist for spiritual or psychological treatment.
Cancer Pain Reduction Goals
Goal is to achieve less pain and suffering. Goal is to obtain informed consent from the patient or legal guardian if life threatening side effects such as bradycardia, hypotension, somnolence and apnea are expected in achieving optimum pain relief. Informed consent and few informative meetings with patient and relatives or legal guardian should eliminate the fear of side effects with adequate pain relief.
Intention is to achieve adequate pain relief with minimum side effects. Intention of physician and nurses is to provide adequate pain relief. Fear of severe side effects leading to fatal outcome hinders provision of adequate pain medications. Lack of knowledge or limited expertise of pain management results in inadequate pain relief and continuation of suffering in several patients.
Objective is to prevent life threatening side effects in underweight terminally ill patients. Objective is to reduce pain to tolerable level, keep patient attentive as much as possible. Patient could thus communicate with families and travel short distance as permitted by disease and side effects. Daily follow up and detailed history should identify patients need of pain.
Investigations for Cancer Pain
- Firstly a physical exam and medical history, history of symptoms help in diagnosing cancer.
- Complete Blood Count, electrolyte levels, other blood studies that may give additional information like PSA or prostate specific antigen test etc.
- Imaging studies such as X-rays, CT and MRI scans, and ultrasound, and endoscopy also help physicians to detect abnormalities in the body that may be cancer.
- Tissue sample such as biopsy gives a definitive diagnosis of cancer. Biopsy can identify the cancer type, and the stage of the cancerous cells.
- In some cases, surgery needs to be done for biopsy and it may result in a cure if all of the cancerous tissue is removed at the time of biopsy.
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