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Year : 2019  |  Volume : 13  |  Issue : 3  |  Page : 263-264

Scope of chronotherapy in managing acute perioperative pain

1 Department of Anaesthesiology, Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
2 Department of Anesthesiology, Sancheti Hospital, Pune, Maharashtra, India

Correspondence Address:
Dr. Abhijit S Nair
Department of Anaesthesiology, Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad - 500 034, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/sja.SJA_827_18

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Date of Web Publication26-Jun-2019

How to cite this article:
Nair AS, Diwan S. Scope of chronotherapy in managing acute perioperative pain. Saudi J Anaesth 2019;13:263-4

How to cite this URL:
Nair AS, Diwan S. Scope of chronotherapy in managing acute perioperative pain. Saudi J Anaesth [serial online] 2019 [cited 2019 Dec 12];13:263-4. Available from:


Chronobiology is a subspeciality of biology that involves understanding biological phenomena which exhibits cyclical behavior. Chronotherapy is a practice in which a particular medication is administered at a specific time of the day so as to have adequate serum concentration, maximal therapeutic effect, and less adverse effects. Chronotherapy advocated administering medications based on the circadian rhythm which is controlled by the suprachiasmatic nucleus located at the base of hypothalamus. Circadian variation leads to alteration in the availability and function of receptors, hormones that eventually affects the pharmacokinetics and pharmacodynamics of the administered drugs. Principles of chronotherapy have been explored, understood, and used successfully in medicine.[1] However, role of chronotherapy in perioperative pain management have not been utilized effectively inspite of lot of animal studies showing circadian changes in nociception.

The reason of cyclic changes in pain perception could be timed release of intrinsic hormones like cortisol, melatonin, and endogenous opioid peptides like metaenkephalin and β-endorphins which can influence the dose and frequency of analgesics especially u-receptor agonists. Other substances that are also involved in pain pathway are bradykinin, 5-hydroxy-tryptamine, glutamate, nitric oxide, substance P, and cytokines. Cortisol peak levels are usually in early morning hours, whereas melatonin exerts its effect at night. Animal studies have shown that analgesia required during these periods is less. Animal data also suggests that there is downregulation of opioid receptors during morning, early afternoon, and late evening hours. Opioid induced respiratory depression in therapeutic doses is also observed more routinely in afternoon when opioid receptors are down regulated.[2] Results of this data could be extrapolated in clinical practice by prescribing opioids when the side effects are less and chances of adverse events are more.

Theoretically pain scores could be higher in day time when patients ambulate or are made to mobilise as a part of physiotherapy. This was observed in certain studies where opioid consumption was found to be more with patient controlled analgesia between 8:00 and 12:00 noon compared to evening and night.[3]

It has been found that if oral nonsteroidal anti-inflammatory drugs (NSAIDs) are administered in the morning there is better absorption, more protein binding which decreases renal toxicity and therefore opioid sparing. Similarly, opioids seems to work effectively when administered in the evening than in morning hours which was also studied in healthy volunteers.[4] These chronopharmacological properties can be used in managing acute postoperative pain quite effectively.

American Society of Anesthesiologists recommends a balanced, multimodal analgesia (MMA) for managing acute postoperative pain.[5] Although opioids and NSAIDs are the cornerstone drugs used in perioperative period; drugs like paracetamol, alpha 2 agonists, N-methyl-D aspartate (NMDA) receptor antagonists, gabapentinoids, dexamethasone, and epidural/peripheral nerve catheter infusion should be used as a part of MMA. Opioids and NSAIDs can be timed according to the hormonal profile so as to have good therapeutic effect and minimal adverse effects. Further studies need to address the appropriate timings wherein other drugs used in MMA can exert better therapeutic effects in combination with opioids and NSAIDs.

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  References Top

Selfridge JM, Gotoh T, Schiffhauer S, Liu J, Stauffer PE, Li A, et al. Chronotherapy: Intuitive, sound, founded…but not broadly applied. Drugs 2016;76:1507-21.  Back to cited text no. 1
Gallerani M, Manfredi R, Dal Monte D, Calo G, Brunaldi V, Simonato M. Circadian differences in the individual sensitivity to opiate overdose. Crit Care Med 2001;29:96-101.  Back to cited text no. 2
Boom M, Grefkens J, van Dorp E, Olofsen E, Lourenssen G, Aarts L, et al. Opioid chronopharmacology: Influence of timing of infusion on fentanyl's analgesic efficacy in healthy human volunteers. J Pain Res 2010;3:183-90.  Back to cited text no. 3
Martin D, McKenna H, Galley H. Rhythm and cues: Role of chronobiology in perioperative medicine. Br J Anaesth 2018;121:344-9.  Back to cited text no. 4
Helander EM, Menard BL, Harmon CM, Homra BK, Allain AV, Bordelon GJ et al. Multimodal analgesia, current concepts, and acute pain considerations. Curr Pain Headache Rep 2017;21:3.  Back to cited text no. 5


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