How Do Long Term Oral Pain Killers Enhance Pain and Promote Chronic Pain?
James D Adams *
PhD, Professor Emeritus, Independent Researcher, Benicia, CA, USA
* Correspondence: James D Adams
Special Issue: Topical Treatment of Pain: Perspectives on Complementary, Traditional, and Plant Medicine
Received: August 01, 2022 | Accepted: August 02, 2022 | Published: August 04, 2022
OBM Integrative and Complementary Medicine 2022, Volume 7, Issue 3, doi:10.21926/obm.icm.2203032
Recommended citation: Adams JD. How Do Long Term Oral Pain Killers Enhance Pain and Promote Chronic Pain?. OBM Integrative and Complementary Medicine 2022; 7(3): 032; doi:10.21926/obm.icm.2203032.
© 2022 by the authors. This is an open access article distributed under the conditions of the Creative Commons by Attribution License, which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.
Abstract
Oral pain medicines are routinely used to treat pain and chronic pain. Recent evidence shows that many of these medicines actually increase chronic pain when used over several weeks. Patients should be encouraged to find alternative pain treatments and avoid oral medicines for pain.
Keywords
Opioids; nonsteroidal anti-inflammatory drugs; pain; chronic pain; chemokines; skin
Chronic pain such as chronic low back pain, whiplash and fibromyalgia affects thousands of patients and can last for several years. Many patients use nonsteroidal anti-inflammatory agents (NSAIDs) or opioids to treat acute and chronic pain. Acetaminophen inhibits cyclo-oxygenase 1 and 2 at the peroxidase site [1] and is therefore an NSAID, although its anti-inflammatory activity is low.
A meta-analysis of 9000 patients found that opioids, NSAIDs, baclofen and duloxetine are effective pain treatments in chronic low back pain [2]. In contrast, a recent study found that long term use of NSAIDs increases pain and promotes the onset of chronic pain [3]. It has been known for sometime that long term use of opioids increases pain, opioid hyperalgesia, and promotes chronic pain [4]. This is especially true of fentanyl and fentanyl patches that can cause hyperalgesia within a few hours of administration [5]. Acetaminophen is not recommended for the treatment of chronic pain [6]. There has been some speculation that neutrophil associated inflammation may be involved in chronic pain induction by NSAIDs [3].
Pain is sensed in the skin by transient receptor potential cation (TRP) channels and other receptors [7,8]. The skin is abundantly endowed with these receptors which makes it exquisitely sensitive to pain. Oral pain killers do not penetrate adequately into the skin to treat severe pain. Oral pain killers poison the body after oral administration, induce respiratory depression, strokes, heart attacks and ulcers that may kill 155,000 people in the US every year [7].
An initial painful insult activates skin sensory neuronal TRP channels, many of which respond to mechanical insults [8]. This damage causes the release of chemokines that attract neutrophils and macrophages. The initial insult may also damage keratinocytes that release bradykinin [9]. Pain, swelling, inflammation and chemokine receptor synthesis are induced by bradykinin. Neutrophils release leukotrienes that activate TRP channels and cause long term pain [7]. Macrophages contain cyclo-oxygense 2 and release prostaglandins that enhance pain and activate TRP channels [7].
Chronic pain is generated in the skin [7]. Chemokines released in the skin activate resident T cells that produce IL-17, which causes bradykinin and chemokine release [10]. This produces more TRP activation, pain and chemokine release. A pain chemokine cycle may be established in the skin, which is the basis of chronic pain.
Opioids induce chronic pain by increasing chemokine synthesis [11]. The synthesis of chemokines in the skin during opioid therapy has not been examined. NSAIDs also increase chemokine synthesis and cause chronic pain. Acetaminophen induced damage to hepatocytes increases chemokine release with the attraction of neutrophils and macrophages [12,13]. Whether this happens in the skin or not has not been examined. Aspirin can induce the synthesis of chemoattractant cytokines, similar to chemokines, in lung tissue [14]. Ibuprofen increases chemokine synthesis and gene expression [15]. NSAID effects on skin chemokines are not yet known. Therapies that inhibit chemokine production [7] are useful in chronic pain.
Author Contributions
The author did all the research work of this study.
Competing Interests
The author has declared that no competing interests exist.
References
- Anderson BJ. Paracetamol (acetaminophen): Mechanisms of action. Paediatr Anaesth. 2008; 18: 915-921. [CrossRef]
- Migliorini F, Maffulli N, Eschweiler J, Betsch M, Catalano G, Driessen A, et al. The pharmacological management of chronic lower back pain. Expert Opin Pharmacother. 2021; 22: 109-119. [CrossRef]
- Parisien M, Lima LV, Dagostino C, El-Hachem N, Drury GL, Grant AV, et al. Acute inflammatory response via neutrophil activation protects against the development of chronic pain. Sci Transl Med. 2022; 14: eabj9954. [CrossRef]
- Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011; 14: 145-161. [CrossRef]
- Mauermann E, Filitz J, Dolder P, Rentsch KM, Bandschapp O, Ruppen W. Does fentanyl lead to opioid-induced hyperalgesia in healthy volunteers? A double-blind, randomized, crossover trial. Anesthesiology. 2016; 124: 453-463. [CrossRef]
- Ennis ZN, Dideriksen D, Vægter HB, Handberg G, Pottegård A. Acetaminophen for chronic pain: A systematic review on efficacy. Basic Clin Pharmacol Toxicol. 2016; 118: 184-189. [CrossRef]
- Adams J. Chronic pain in the skin and neurogenic inflammation. J Altern Complement Integr Med. 2019; 5: 073. DOI: 10.24966/ACIM-7562/100073. [CrossRef]
- Nilius B, Owsianik G, Voets T, Peters JA. Transient receptor potential cation channels in disease. Physiol Rev. 2007; 87: 165-217. [CrossRef]
- Koyama S, Sato E, Nomura H, Kubo K, Miura M, Yamashita T, et al. Bradykinin stimulates type II alveolar cells to release neutrophil and monocyte chemotactic activity and inflammatory cytokines. Am J Pathol. 1998; 153: 1885-1893. [CrossRef]
- McGeachy MJ, Cua DJ, Gaffen SL. The IL-17 family of cytokines in health and disease. Immunity. 2019; 50: 892-906. [CrossRef]
- Qiang Z, Yu W. Chemokine CCL7 regulates spinal phosphorylation of GluA1-containing AMPA receptor via interleukin-18 in remifentanil-induced hyperalgesia in rats. Neurosci Lett. 2019; 711: 134440. [CrossRef]
- Jaeschke H, Ramachandran A. Mechanisms and pathophysiological significance of sterile inflammation during acetaminophen hepatotoxicity. Food Chem Toxicol. 2020; 138: 111240. [CrossRef]
- James LP, Mayeux PR, Hinson JA. Acetaminophen-induced hepatotoxicity. Drug Metab Dispos. 2003; 31: 1499-1506. [CrossRef]
- Teran LM, Ramirez-Jimenez F, Soid-Raggi G, Velazquez JR. Interleukin 16 and CCL17/thymus and activation-regulated chemokine in patients with aspirin-exacerbated respiratory disease. Ann Allergy Asthma Immunol. 2017; 118: 191-196. [CrossRef]
- Wang XM, Wu TX, Hamza M, Ramsay ES, Wahl SM, Dionne RA. Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007; 128: 136-147. [CrossRef]
