Modern strategies for pain management RESEARCH PAPER Ebuka Ibuoka, Varshini Sridhar, Victoria Ijezue, Unyime Ibanga, Emem Abasiekong, Dr. Esther Olunu Abstract Pain, as a concept is one of the most congruent human sensations, has the unusual ability to vary across races, gender, class and from the moment we are born to the moment we die, we are experiencing one kind of pain or the other. Pain, especially chronic pain, forces our ability to act in standard, coherent ways to be affected to the point where we no longer function. However, no matter how congruent, the idea of pain remains an ever-changing field of extensive studies on treating, managing, and understanding pathways of pain. Pain is as much a part of human history as time, therefore an understanding of the past, i.e., how pain has been treated historically needs to be juxtaposed with how management of pain has changed with the rapid scientific advancements the world has seen in the last two centuries, medically and pharmacologically is what the paper is about. Almost equally as important are new ideas like using natural remedies involving the cannabis industry and old Asian techniques like acupuncture, which are fringe but relatively effective management strategies that might change the way we look at pain forever. Ultimately note that the role of modern pain management strategies depends significantly on the evidence of their effectiveness in subverting pain and distress, and in improving quality of life. Methodology: Well established and stipulated search criteria is necessary for any good review and on this paper, we sourced a large amount of data from scientific journals and as much as possible, from the most recently published papers in the field. We picked the data sources from a variety of pain articles dedicated to different areas of pain. Reports ranging from treatment of cancer pain to cystic fibrosis were essential to get a better all-around view of pain management. Search organization: The research team conducted searches on multiple broad criteria before being whittled down to the most centrally relevant articles. These are the search criteria: 1. Year of publication. Majority of the paper focuses on modern strategies. However, there is a sizeable portion of the research conducted on previous pain management strategies in history. Therefore, we did not have restrictions on the years of publication beneficial to the study at hand. On an excellent paper of scientific basis, emphasis must be placed on up to date research as much as possible to avoid as many errors as one can. Thus, the focus searching through articles in the last ten years. Mainly articles between 2008 and 2018 were eventually used for relevance. 2. Source of the article. Even more important than the year of publication is the source of writing. To keep this paper as relevant as possible, we worked mainly through PubMed and a few other scholarly journal archives like ScienceDirect and even google scholar while making sure to use criteria like the year of publication, type of publication and scientific relevance as filters. Search words: To keep the paper and themes incongruence, we used specific words and phrases as the backbone of our online and textbook searches. Specifics are Words like Pain, management strategies for pain, strategies for managing pain. Pain in different illness and the treatment. While streamlining, phrases like fringe methods for managing pain, articles on pain and history of pain were also used to fund the discussions component of this paper to explore the main ideas of this publication fully To maintain the integrity of this article, we followed strict guidelines. Introduction : This paper aims to delve into the idea of pain as a concept and the treatment of pain. In the paragraphs below, we aim to achieve a comprehensive review of articles and research centered around pain management, its history and the current needs and processes of understanding the pain and managing it in acute and chronic patients. Pain management has advanced incredibly in the past century with the industrialization of many developed nations and innovations in drug synthesis. It is also important to note how pain was treated in the past and throughout history. Not only is it pertinent to this discussion to understand how we have treated pain historically, but it also cuts across how medicine itself has evolved. Currently, we have a myriad of pain treatment and management options that are always changing as technology changes. A lot of the management possibilities we have today are still not very efficient, however, and sometimes the incidence and prevalence of diseases and chronic pain in our society seems to surpass the reach of technology and medicine. It is then essential to talk about how pain management can improve in ways that it benefits the most people as much as possible with the most efficiency, especially without addiction, as has been the case with drugs such as opioids and morphine. Classification and understanding of pain Pain is a complicated sensation felt by individuals experiencing damaged tissues at a cellular level (1,6,7,8,9,10,11). The cause of pain is usually a damaging stimulus described as nociceptive and through various complications such as stepping on a nail, experiencing a burn, applying alcohol to a cut, etc. 1,6,7,8,9,10,11 We can typically classify pain as chronic or acute depending on the longevity and the incidence of the discomfort. Referred pain is a mixture of somatic and visceral nociceptive inputs on the same projection in the neuron in which the pain does not know the source of the pain (43). Acute pain, also known as sharp, throbbing, burning and unusual sensations that increase our blood pressure and heart rate at a specific point in time (1). It rarely lasts for more than six months in duration. From time to time, individuals experience acute pain - such as a deep paper cut, sudden temperature changes on the skin, toothaches, etc. Acute pain can be further subcategorized (Figure 1.0).Some patients experiencing severe pain respond well to medication and are advised to follow the R.I.C.E. method of healing comprised of R-Rest, I-Ice, C-Compression, and E-Elevation (2). Chronic pain refers to unease caused for weeks, months or even years after an injury lasting anywhere from three to six months in length (4). Some may experience chronic pain caused by trauma, metabolic causes, toxicity, pathogenic, autoimmune disease, etc. (43). The unusual feeling arises when the signals are sent to the nervous system and stimulate the pain receptors in the somatosensory cortex of the brain (5). This kind of pain affects around 20% of the population and is hugely detrimental to the quality of life (43). The signals received from the source of pain go in the form of an electrical signal traveling nerve to nerve until it reaches the brain and becomes a habit of repeated receptors stimulus (1). The ganglia that the pain reaches innervates only certain areas of the periphery (43). Within the ascending pathways, we have categories of spinothalamic, spinoreticulothalamic and spinomesencephalic pathways where each innervates various responses of the body. This continuous inducement becomes chronic over time without any initial injury to the affected area and can range from mild to severe in extent over time. Some people may experience pain as just one of their many symptoms. However, it is vital to know the etiology to diagnose the issue successfully. Instances of irritation in the endometrium of the uterus, fibromyalgia, inflammatory bowel disease of the digestive tract, and temporal-mandibular joint dysfunction of the jaw may be a cause of discomfort due to previously diagnosed health conditions (2). There are certain conditions in which discomfort may persist nevertheless due to no known injuries. For that, we use the term idiopathic. For example, some idiopathic causes of pain include the sense of feeling fatigued, hungry, trouble sleeping, mood changes, weakness and lethargic. Figure 1.0-Types of Acute pain Name Description Chest Pain Sharp to a dull pain that radiates up the neck and pierces through the back and down one or both arms. Can be described as crushing or burning. Sometimes may involve the heart or lungs. Myocardial Infarction Heart Attack Depression Weakness Reduced range of motion Also known as reflective pain and is identified at other locations other than the site of stimulus. Radiation and referred pain are distinguished based on movement. Referred pain is when the pain is away from the site of stimulus, and radiating pain is when the pain changes position from the organ involved. Hard to focus Exhaustion Unfocused Ischemia due to Myocardial Infraction Stiffness Soreness Squeezing Referred Pain Effect REF (2) (2) Anesthesia Dolorosa Anesthesia blocks pain in a specific location can be generalized or regional in which it provides a loss of sensation by reducing nerve activity until the procedure (i.e., surgery) finishes. Headaches Forgetfulness A sore throat Confusion (2) Figure 1.1- Types of Chronic pain Name Description Muscle Knots Muscle fibers that stick together and adhere to each other, creating a hard and lumpy feeling known as a “Knot.” Myalgia Dehydration and Diet Lifestyle Issues Loss of energy, with prolonged weakness Insomnia Brain Inflammation Infections Peripheral Edema Hot Flashes Chronic Fatigue Syndrome Endometriosis Uterine lining grows outside the uterus Effect REF (2) (2) (2) Fibromyalgia Neuropathic pain Pain in the bone and muscles Damaging the nervous system Muscle Tension Stiffness Depression Anxiety Anger (2) (2) A category of the projections of neurons transmits information into the SCC= location and intensity. There are the cingulate, and insular cortices via the PBN and amygdala together called the affective component as well as the ascending pain information links with neurons in the RVM and PAG collectively known as the descending control systems (43). The mechanisms of pain can be categorized based on the pathways in which it alters the function of the brain. Nociception can fall under the characteristics of anatomical and molecular groups ( figure 1.1 added below) (43). Nociception is the usual response to pain management by the body itself without external factors involved (3). Nociceptors fall under a subcategory of pain, and they express unique transductory signals and molecules associated with a stimulus. Its central role is to activate various stimuli ranging from mechanical to thermal, thermal to electrical, innervating the skin, viscera, muscles, joints, and meninges. Peptidergic C is composed of neuropeptides and TrkA molecules and Non-peptidergic C bind IB4 and express c-Ret, Mrg GPCR’s, and purinergic receptors including P2X3; additionally, we have a differential expression of channels that are critical for transducing heat composed of TRPV1, cold composed of TRPM8, acids formed of ASIC’s and chemicals comprising TRPA1 (43). In situations where there is neurogenic inflammation, the direction of current passing can be distinguished by the afferent pathway which is towards the CNS and efferent which is away from the CNS. Furthermore, the inflammation that occurs at this site is called the axon reflex because it can occur without contribution from the CNS (43). The two distinguishable fibers that conduct the stimuli are through C fibers and A-delta fibers along with A-beta fibers. HTM’s include C fibers and AM fibers, while LTM’s include A-delta fibers and A-beta fibers. The LTM’s also contain Meissner and Merkel cells, and Pacinian and Ruffini corpuscles and hair follicles which detect texture, vibration, light, and pressure (43). Alpha-Delta fibers are lightly myelinated and conduct signals at a rapid rate and are sharper in response to mechanical and thermal stimuli (in particular). C fibers are slow conducting fibers due to their unmyelinated signal conduction pathway system which consists of proteins in the membrane of the receptors (4). They are known as polymodal, meaning multiple stimulus modalities are involved; responding specifically to thermal, chemical and mechanical stimulus. Inflammatory mediators such as bradykinin, prostaglandins, cytokines, H+, and serotonin are all stimulatory by releasing from damaged tissue in response to an injury (5). The activation of voltage-gated channels leads to a stimulation of action potentials to initiate the electrical singling into the nervous system, which then enhances the cells behavior and types of channels present in the nociceptor to reduce the level of discomfort. The neuronal arrangement at each synapse in these pathways is essential for processing the information. Whether it is through convergence in signals from various neurons synapse with a single neuron or divergence in which there are signals from one neuron transmitted to others, and that gets amplified. In lateral inhibition, signals get passed on from one neuron to another to inhibit the nearby neurons; this enhances contrast. The transmission of pain is mainly through the change in voltage across the membrane potential; this then intensifies and determines the frequency of action potential firing through the voltage-gated ion channels (43). Sometimes, the ectopic neuronal activity may occur in which after an injury, there is an increased expression of sodium channels and a reduction in potassium channels that generate enough action potentials to cause spontaneous activity. Also, there may be abnormal connections where the rewiring of the circuit may contribute to continuous pain hypersensitivity cause sprouting of sympathetic neurons in the DRG to cause neuropathic pain (43). Pain also travels through the central nervous system and passes through the dorsal grey horn of the spinal cord. The mechanism is known as the gaiting theory. This process happens by stimulating the somatosensory input to the projector neurons(6). There are nerve gates that need to be passed to reach the brain. What happens is by closing this gate and inhibiting interneurons which decrease transmission of the nociceptive signals that get sent to the thalamus, you get diminished pain. Figure 1.2 explains the appropriate scheme in which pain is perceived and transmitted. As injury persists, the microgliamacrophages of the CNS accumulate and induce various molecules including cytokines to enhance central sensitization. For example, CX3CL1 is released and acts on CX3CR1 on the glia (43). Astrocytes are also activated, and this is delayed and persists longer in the maintenance of central sensitization and persistent pain. According to Sarah Lawson, the author of Fundamentals of nursing: Factors affecting individualized responses to pain. Woman have a lower pain threshold compared to men who have a much higher distinguishable range of pain thresholds which directly relates to lifestyle including their daily diet, age, gender, and physical factors. (7) Pain sensations and elements are what distinguishes how different people respond to different kinds of pain. For example, an adolescents’ pain tolerance may be high in comparison to an elderly aged 65+ overcoming the same stimulus of psychogenic pain (i.e., a headache). An athletic, trained individual compared to an obese individual sensing nociceptive pain such as falling off a chair will have different responses (8). When a patient complains that they have pain, that is subjective. However, if while an attending physician is examining the patient and then the patient complains of pain, that is said to be objective. Pain management is a method of appointing an interdisciplinary approach to revealing the illness and improving the quality of life using various strategies. In previous decades, one of the main complaints of returning patients was that they faced difficulties managing pain, but in recent studies, there is evidence that one can better manage pain through by various methods (12, 13, 14, 15) Addressing the treatment of pain The American Board of Pain Medicine(2011) states that you can treat pain in several ways including evaluations, rehabilitation processes, comprehensive care, and physician aid. For many individuals, pain can be a disease, a symptom or as both. For a physician to treat a patient’s discomfort, there must be effective pain management techniques, patient-centered communication, and education. Furthermore, Methods to manage and address pain vary from psychological to physical to the chemical. The role of psychosocial interventions in the management of patients is concerned with pain assessment scales and non-verbal cues. These can be used to help those who are unable to report their pain sensations (40). Also, communication with close family and caregivers could potentially be an avenue for pain reporting. Psychiatrists are encouraged to request patients to provide self- reports of pain as they are the most reliable pain indicator. Also, during the patient’s report, questions relating to their symptoms will allow patients to relay communication to the doctor so that the treatment plan can go along with the best conclusion of their diagnosis. Listening to the patient’s feelings and analyzing their stories allows the Doctor or psychologist to educate the patient, guiding them to a more educated decision towards taking the next step in their pain management. Also, note that increasing K channel activity could potentially treat persistent pain. However, besides treating pain by a psychological means, patients have often prescribed drugs as a method of treatment(40). Beneficial psychological approaches to managing pain include treatments that increase selfmanagement, changes in behavior and cognitive changes rather than directly elimination of pain at a locus. Psychologists can also try to alleviate pain symptoms in patients by increasing pain-coping resources and reducing emotional distress. Through the implementation of non-chemical steps like the above, psychologists can effectively help patients feel more in control enabling them to live a normal life despite their pain as well as ensure that they become more active in the management of their illness in a way they can employ throughout their lives (41). In contrast, some drugs that doctors prescribe could potentially cause brain damage leading to maladaptive behavior as an effect of the medication that may interfere with normal physiology. (42) History of pain management The phenomenon of pain and its understanding was affected by culture and infringed on the methods used in its control (31). Before the introduction of anesthesia (a sedative ether gas) in 1846, surgeons used to take pride in operating within a limited time to minimize patients' agony (32). The use of anesthesia was opposed by some medical factions, especially among doctors who were not enthusiastic about a sedative which could render a patient unconscious during a procedure — Doctors who were worried about operating considered this a source of considerable debate. By the 19th century, Doctors began using opiates (opium) in the treatment of acute and chronic conditions such as Injury related pain, headache, toothache, gastric pain, dysentery, diarrhea, and smallpox. In 1840, morphine, a derivative of opium, was industrially manufactured in Germany by Friedrich Serturner (33). It changed the pain treatment landscape, and the use of morphine became global with the invention of hypodermic needles (34). Morphine administered subcutaneously was believed to be void of the side effects accrued with oral opiate consumption. However, the absence of morphine regulation and the presence of hypodermic needles led to its overuse and abuse. By the 1870s, physicians had witnessed the effects of opium abuse on the physical and mental wellbeing of individuals (35). Following morphine addiction, diacetylated-morphine was manufactured to help in pain management. After studies of its effect on different animal groups, there was a realization that diacetyl-morphine was more effective in the treatment of respiratory complications such as a cough and less effective in pain management. Diacetyl-morphine under the registered name heroin was believed to be less addictive than codeine and became a morphine substitute. Just like morphine, heroin became a drug of abuse but was even more potent. With the innovative means of pill-crushing (breaking down of tablets into half size or powder), people could sniff or smoke Heroin. Heroin abuse led to strict government regulations in the USA promoting the limited production of heroin and guiding against illegal production of opium, morphine, cocaine and other substances (31,35,36). Due to scientific progress made, a various semisynthetic and synthetic derivative of morphine and codeine such as hydromorphone, dihydrocodeine, hydrocodone, oxymorphone became new opioid analgesics (38). By 1953, production started on fentanyl, a drug 40 times more active than morphine in relieving pain. The understanding of the pharmacokinetics and dynamics of Fentanyl led to the manufacture of more potent analgesics such as carfentanil, sufentanil, alfentanil (39) In the 19th and 20th century, scientists began synthesizing non-opioid drugs from the bark of willow trees. The drugs like aspirin (NSAIDs) are antiphlogistic (capable of reducing inflammation), antipyretic (reducing fever) and analgesic (Pain relief). Also, Other NSAIDs, there was the introduction of drugs such as indomethacin and ibuprofen for the treatment of rheumatoid arthritis and pain. MODERN STRATEGIES FOR THE MANAGEMENT OF PAIN Central sensitization is a mechanism of the nervous system that deals with and is concerned with chronic pain and how it progresses and is managed over time (30). Once activated the nervous system goes to a state of high reactivity where it lowers the threshold for pain (30). This mechanism has a very crucial part to play in post-surgical and post-traumatic pain. Central sensitization has two types: allodynia and hyperalgesia (25,30). In allodynia, the patient experiences pain to harmless stimuli like massage or a simple touch on the skin that they usually won't feel pain to (30). This feeling is due to the heightened sensitivity of the nervous system and release of specific sensitizers like PGEs, leukotrienes, bradykinin, etc. (25). Hyperalgesia, however, has to do with increased response to pain, things that may typically cause pain like a nail prick, these patients feel this pain a lot worse. Primary hyperalgesia is due to the response from peripheral pain receptors while secondary hyperalgesia is due to the reaction of the spinal cord and CNS (25,30). Neurokinin receptor (NK1) and cyclooxygenase-2 (COX 2) have to do with central sensitization (25). Understanding this mechanism of pain has led to the establishment of multimodal analgesia and new pharmaceutical products to treat pain (25). Two significant advances are the development of extended-release epidural morphine (EREM) and iontophoretic transdermal fentanyl. EREM makes use of a system known as DepoDur to provide longerlasting pain relief within 48hrs after initial dosage (25). This technology combines extended analgesia with epidural morphine and is administered epidurally at the lumbar region. It yields lesser side effects of nausea, vomiting, sedation, constipation, enhances pain relief and provides extended analgesia even in the absence of opioids and enhances patients' activity levels. It is in use in knee surgeries, and cesarean operations and various studies have shown that it yields longer and extended pain relief. Common side effects that can arise from the administration of EREM are pruritis (or severe itching) and respiratory depression seen in about 12% of patients, which opioid antagonists treat. Note that the elderly are more susceptible to these side effects and should be monitored closely upon administration (25). Fentanyl iontophoretic transdermal system is the new patient-controlled analgesia (PCA) that uses iontophoretic technology to administer fentanyl across the skin and into the systemic circulation by applying a low-intensity electric field (25,29). It has been approved for use to treat acute, moderate to severe postoperative pain in the USA and Europe (29). Unlike other PCAs which have provided limitations like programming errors, reduced patient's mobility due to pumps, lines, and tubing, fentanyl it gives the patient the opportunity to administer pre-programmed doses of fentanyl non-invasively to themselves using iontophoretic technology and its method of delivery prevents risks of complications, programming errors and overdose (25,29). Its effectiveness has been demonstrated to be like morphine IV-PCA producing similar side effects as IV opioid administration. These side effects include nausea (most common, affecting about 26-67% of patients), vomiting, pruritis, headache, and dizziness. Skin hypersensitivity, skin redness and hyperpigmentation like other transdermal systems are possible problems that can occur. The system has not been thoroughly studied and understood in children and should be used cautiously in patients with severe hepatic dysfunction, head injuries, sleep apnea, imminent respiratory failure and increased intracranial pressure of any cause (25). Other pharmacological products that are in development for the management of pain are: 1. Analgesic adjuvants: adjuvants are being developed for the management of postoperative pain to prevent unfavorable side effects of opioid analgesics which delay recovery. Although when administered separately, it is not as effective when mixed with opioids, it provides better pain relief with less unfavorable side effects (25). 2. Capsaicin: and several related compounds called capsaicinoids is an analgesic found in seeds and stem of chili peppers that acts on TRPV-1 as an agonist (25). TRPV-1, transient receptorpotential cation-channel subfamily V member 1’ receptors are present in nociceptive neurons of the peripheral nervous system, on unmyelinated C fibers and are involved in the transmission and modulation of pain. Capsaicin as a TRPV-1 agonist acts to activate TRPV-1 to release substance p which produces the initial feeling of “burning.” Subsequent activation of TRPV-1 with the prolonged discharge of substance p in the presence of capsaicin results in the exhaustion of available capsaicin and an eventual reduction in activation of the c fibers. You can administer capsaicin topically or intravenously, and it acts peripherally. Topical capsaicin can be applied in combination with narcotic analgesics and NSAIDs to provide relief for back pain, arthritic joint aches, sprains, and strains and can be an adjuvant for the elderly (25). IV capsaicin is used to manage postoperative pain. It is important to note that capsaicin is inadvisable to use in patients age less than 2, with elevated liver enzymes, those on ACEI and patients with signs of joint infections and septic arthritis. 3. Ketamine: This is an NMDA antagonist used in low doses in the clinic as an analgesic in the control of pain before, during and after surgery. It is usually injected into the muscle or given through IV, and it provides relaxation and pain relief. Its use is currently in restriction due to the adverse side effects associated with its use. Common side effects include hallucinations, dizziness, blurred vision, nausea, and vomiting. It can produce feelings of dissociation when abused. 4. Gabapentin and Pregabalin: Gabapentin has been shown to be useful in diabetic neuropathy, post-herpetic neuralgia, and neuropathic pain. Its analog pregabalin is also an anesthetic and sedative. Studies are still ongoing for their use as multimodal analgesia. Their opioid-sparing effect has shown to be helpful in the management of acute and postoperative pain (25). Other pharmacological products recently in use for the management of pain are local anesthetics, Dexmedetomidine, and tapentadol. Attention is also coming back to other pharmacological methods which were previously in use like NSAIDs, coxibs, and acetaminophen (25). Development of newer surgical techniques with less invasive methods like arthroscopic surgery, eye surgery, laparoscopic cholecystectomy, sterilization procedures has also helped to minimize postoperative pain and complications and reduce the length of hospital stay and recovery time (26). Apart from pharmacological therapies, there is also increasing awareness of nonpharmacological methods like acupuncture, herbs, magnets, hypnosis which can yield maximum pain relief with lesser side effects and future complications (25,27). Fringe approach to pain management Music Music and other fringe pain management tools are used to change the perception of pain in patients. Music does not stop the pain; rather, music could modify how a patient feels. Most notably according to Bernatzky on “Emotional foundations of music as a non-pharmacological pain management tool in modern medicine” patients have reported during the stress of surgery, that music stimulation reduces the way they feel pain. It can be a stand-alone method or included in a multimodal pain management program, Ultimately music and other fringe methods for pain management reduce the need for pharmaceutics which has major side effects and can be detrimental in the same vein that they are helpful. (16,19,20) Psychological interventions Psychological interventions are a new but very useful tool of modern pain management practice and an endorsed feature of current pain treatment service. The evidence for effectiveness is most significant for cognitive behavioral therapy (CBT) with an emphasis on cognitive coping strategies and behavioral rehearsal. It is possible to cause changes in pain, mood, and disability by this type of treatment. However, the overall results of procedures using CBT for adults, across all trials, have been modest so it is still new to most people and further research needs to be performed(17,20). CBT Cognitive behavioral therapy has been proven to be effective in reducing pain immediately after treatment compared with doing nothing, but the effect is minimal in the grand scheme. That is, Behavior therapy has no real objective impact on pain. However, CBT has been found to be effective in reducing disability or at least the perception of immediately after treatment, even without long-term results. (17). Overall, the findings for behavioral therapies are promising. And can lead to positive changes in the future Cannabinoids Cannabinoids for cancer pain are relatively new, and there is growing excitement among the public, especially for patients who have used, or experienced cannabis-induced pain relief. However, the term “medical marijuana” can be confusing. It encompasses endogenous cannabinoids, plant-derived cannabinoids—such as tetrahydrocannabinol (THC) and cannabidiol (CBD)—and synthetic cannabinoids: nabilone and dronabinol. There is a huge difference between THC and CBD, and although the latter is not concerned with hallucinations or the high induction capabilities of THC, it has not been studied well enough or long enough to be fully confirmed as a beneficial treatment possibility for chronic pain, especially cancer pain. (21,22) Acupuncture Many cancer centers offer acupuncture as part of their services. At this time, a comprehensive systematic review of acupuncture in cancer care has not occurred. However, a few studies have been conducted, albeit on small groups of people. (18) The studies include people with pain involving symptoms like nausea, hot flashes, fatigue, radiationinduced xerostomia, prolonged postoperative ileus, anxiety/ mood disorders, and sleep disturbance. About half of the trials resolved with positive results, but the other half had little to no observable, gradable change in pain. Conclusion: Acupuncture is a good alternative treatment for chemotherapy-induced nausea/vomiting and pain, but further research and studies are required. For many other symptoms or types of pain of the chronic or acute kind, the efficiency of acupuncture as a treatment method remains unknown due to the lack of current objective understanding of the field. Future research should focus on standardizing comparison groups and treatment methods, should be at least single-blinded, compare to biologic mechanisms, increase or level statistical power, and should use multiple acupuncturists. (18,23,24) Acknowledgments All Saints University school of medicine Dr. Esther Olunu (Research Professor, Professor of Embryology and Microbiology, All Saints University School of Medicine, Dominica) References 1. Muhammad S. What is Pain/Types of Pain Treated? [Internet]. Johns Hopkins Medicine Health Library. 2017 [cited 2018Jul3]. Available from: https://www.hopkinsmedicine.org/pain/blaustein_pain_center/patient_care/what_is_pai n.html 2. Deardorff WW. Types of Back Pain: Acute Pain, Chronic Pain, and Neuropathic Pain [Internet]. Spine-health. [cited 2018Jul3]. Available from: https://www.spinehealth.com/conditions/chronic-pain/types-back-pain-acute-pain-chronic-pain-and-neuropathicpain 3. Garner W. Acute vs. Chronic: Understand Your Pain [Internet]. Advanced Pain Care. 2015 [cited 2018Jul3]. Available from: https://austinpaindoctor.com/blog/acute-vs-chronicunderstand-your-pain 4. Epidemiological features of chronic low-back pain [Internet]. Egyptian Journal of Medical Human Genetics. Elsevier; 1999 [cited 2018Jul3]. Available from: https://www.sciencedirect.com/science/article/pii/S0140673699013124 5. McAllister MJ. On the Meaning of "Chronic" [Internet]. Institute for Chronic Pain. [cited 2018Jul3]. Available from: http://www.instituteforchronicpain.org/understandingchronic-pain/healthcare-system-failings/the-meaning-of-chronic 6. Pain and Disability [Internet]. Google Books. Google; [cited 2018Jul3]. Available from: https://books.google.dm/books?hl=en&lr=&id=6jQrAAAAYAAJ&oi=fnd&pg=PA1&dq=pain defined in medicine &ots=ZomRHAmy2i&sig=nxG4MhFxkC4_lsucbvoM6JrWMQ8&redir_esc=y#v=onepage&q=pain defined in medicine&f=false 7. Ford. Columbia University, New York, NY, USA. ford@movdis.cis.columbia.edu [Internet]. Health Communication. Oxford Pharma Genesis, Oxford; 1998 [cited 2018Jul3]. Available from: http://europepmc.org/abstract/med/10785830 8. Imani F, Safari S. [Internet]. U.S. National Library of Medicine; 2011 [cited 2018Jul3]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335733/ 9. Livingston, W. K. “What Is Pain?” Scientific American, vol. 188, no. 3, 1953, pp. 59–67., www.jstor.org/stable/24944158. 10. Woolf CJ. What is this thing called pain? [Internet]. The Journal of Clinical Investigation. American Society for Clinical Investigation; 2010 [cited 2018Jul3]. Available from: https://www.jci.org/articles/view/45178 11. What is a 'clinically meaningful' reduction in pain? : PAIN [Internet]. LWW. Oxford University Press; [cited 2018Jul3]. Available from: https://journals.lww.com/pain/Citation/2001/11000/What_is_a__clinically_meaningful__ reduction_in.3.aspx 12. Pain Management: A Fundamental Human Right : Anesthesia & Analgesia [Internet]. LWW. Oxford University Press; [cited 2018Jul3]. Available from: https://journals.lww.com/anesthesiaanalgesia/Fulltext/2007/07000/Pain_Management__A_Fundamental_Human_Right.37.aspx 13. Phillips DM. JCAHO Pain Management Standards Are Unveiled [Internet]. JAMA Internal Medicine. American Medical Association; 2000 [cited 2018Jul3]. Available from: https://jamanetwork.com/journals/jama/article-abstract/2552036 14. Dolin S, Cashman J, Bland J. Effectiveness of acute postoperative pain management: I. Evidence from published data. British Journal of Anaesthesia [Internet]. 2002 [cited 3 July 2018];89(3):409-423. Available from: https://bjanaesthesia.org/article/S0007-0912(17)374226/abstract 15. Jones L. Pain management for women in labor: an overview of systematic reviews [Internet]. Freshwater Biology. Wiley/Blackwell (10.1111); 2012 [cited 2018Jul3]. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1756-5391.2012.01182.x 16. Bernatzky G, Presch M, Anderson M, Panksepp J. Emotional foundations of music as a nonpharmacological pain management tool in modern medicine. Neuroscience & Biobehavioral Reviews. 2011;35(9):1989-1999. 17. Eccleston C, Morley S, Williams A. Psychological approaches to chronic pain management: evidence and challenges. British Journal of Anaesthesia [Internet]. 2013 [cited 9 June 2018];111(1):59-63. Available from: http://bjanaesthesia.org 18. Garcia M, McQuade J, Haddad R, Patel S, Lee R, Yang P et al. Systematic Review of Acupuncture in Cancer Care: A Synthesis of the Evidence. Journal of Clinical Oncology [Internet]. 2013 [cited 9 June 2018];31(7):952-960. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577953/ 19. Holden R, Holden J. Music: a better alternative than pain? British Journal of General Practice [Internet]. 2013 [cited 2 July 2018];63(615):536-536. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782778/ 20. Williams A, Eccleston C, Morley S. Psychological therapies for the management of chronic pain (excluding headaches) in adults. Cochrane Database of Systematic Reviews [Internet]. 2012 [cited 2 July 2018]; Available from http://cochranelibrarywiley.com/doi/10.1002/14651858.CD007407.pub3/abstract;jsessionid=A 4BEAAA38309022F4CFBCEE7B9F33F2A.f01t02 21. Ware M, Wang T, Shapiro S, Collet J, Boulanger A, Esdaile J et al. Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). The Journal of Pain [Internet]. 2015 [cited 2 July 2018];16(12):1233-1242. Available from: https://www.sciencedirect.com/science/article/pii/S1526590015008378 22. Hill K, Palastro M, Johnson B, Ditre J. Cannabis and Pain: A Clinical Review. Cannabis and Cannabinoid Research [Internet]. 2017 [cited 2 July 2018];2(1):96-104. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549367/ 23. Ning Z, Lao L. Acupuncture for Pain Management in Evidence-based Medicine. Journal of Acupuncture and Meridian Studies [Internet]. 2015 [cited 2 July 2018];8(5):270-273. Available from: https://www.sciencedirect.com/science/article/pii/S2005290115001545 24. Wilkinson J, Faleiro R. Acupuncture in pain management. Continuing Education in Anaesthesia Critical Care & Pain [Internet]. 2007 [cited 2 July 2018];7(4):135-138. Available from: https://academic.oup.com/bjaed/article/7/4/135/466586 25. Nalini Vadivelu D. Recent Advances in Postoperative Pain Management [Internet]. PubMed Central (PMC). 2018 [cited 2 July 2018]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844689/ 26. 26 Wilmore D. Recent advances: Management of patients in fast-track surgery. BMJ [Internet]. 2001 [cited 2 July 2018];322(7284):473-476. Available from: https://www.bmj.com/content/322/7284/473.short 27. Chaves J. Recent Advances in the Application of Hypnosis to Pain Management. American Journal of Clinical Hypnosis [Internet]. 1994 [cited 2 July 2018];37(2):117-129. Available from: https://www.tandfonline.com/doi/abs/10.1080/00029157.1994.10403124 28. Lucas L, Lipman A. Recent Advances in Pharmacotherapy for Cancer Pain Management. Cancer Practice [Internet]. 2002 [cited 2 July 2018];10(s1):s14-s20. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1523-5394.10.s.1.6.x 29. Power I. Fentanyl HCl iontophoretic transdermal system (ITS): clinical application of iontophoretic technology in the management of acute postoperative pain. British Journal of Anaesthesia [Internet]. 2007 [cited 2 July 2018];98(1):4-11. Available from: https://bjanaesthesia.org/article/S0007-0912(17)35289-3/fulltext 30. Murray J. McAllister P. What is Central Sensitization? [Internet]. Instituteforchronicpain.org. 2018 [cited 2 July 2018]. Available from: http://www.instituteforchronicpain.org/understandingchronic-pain/what-is-chronic-pain/central-sensitization 31. Morris DB. The Culture of Pain. Berkeley: University of California Press; 1991. 32. Meldrum M. A Capsule History of Pain Management. JAMA. 2003;290(18):2470. 33. Völger G. Rausch und Realität - Drogen im Kulturvergleich. Rautenstrauch-Joest Museum: Köln, 1981. 34. Schulte is Esch J, Goerig M. The history of anesthesia. Dräger: Lübeck, 1997. 35. Balthasar Hv. Ed. Die großen Ordensregeln. 3. Ed. Johannes-Verlag: Einsiedeln. 1974. 36. Levinthal C. Milk of paradise/milk of hell - the history of ideas about opium. Perspect Biol Med 1985; 28: 561-77. 37. Sneader W. The discovery of heroin. Lancet 1998; 352: 1697-9. 38. Waldvogel H. Analgetika, Antinozizeptiva, Adjuvantien. Handbuch für die Schmerzpraxis. Springer Verlag: Berlin, 1996. 39. Janssen P, Jageneau H. A new series of potent analgesics: Dextro2:2-diphenyl-3-methyl-4morpholinobutyrylpyrrolidine and related basic amides. J Pharm Pharmacol 1958; 10: 14-21. 40. Kraft C. Overcoming Barriers to Pain Management [Internet]. prezi.com. 2014 [cited 2018Jul4]. Available from: https://prezi.com/soyxq-etmy8m/overcoming-barriers-of-pain-management/ 41. Roditi D, Robinson ME. [Internet]. Psychology research and behavior management. Dove Medical Press; 2011 [cited 2018Jul4]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218789/ 42. Benefits and Risks of Opioids for Chronic Pain Management [Internet]. Arthritis Information. [cited 2018Jul4]. Available from: https://www.hopkinsarthritis.org/patient-corner/diseasemanagement/benefits-and-risks-of-opioids-for-chronic-pain-management/ 43.