Postoperative pain-from mechanisms to treatment

Esther M Pogatzki-Zahn, Daniel Segelcke, Stephan A Schug, Esther M Pogatzki-Zahn, Daniel Segelcke, Stephan A Schug

Abstract

Introduction: Pain management after surgery continues to be suboptimal; there are several reasons including lack of translation of results from basic science studies and scientific clinical evidence into clinical praxis.

Objectives: This review presents and discusses basic science findings and scientific evidence generated within the last 2 decades in the field of acute postoperative pain.

Methods: In the first part of the review, we give an overview about studies that have investigated the pathophysiology of postoperative pain by using rodent models of incisional pain up to July 2016. The second focus of the review lies on treatment recommendations based on guidelines and clinical evidence, eg, by using the fourth edition of the "Acute Pain Management: Scientific Evidence" of the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine.

Results: Preclinical studies in rodent models characterized responses of primary afferent nociceptors and dorsal horn neurons as one neural basis for pain behavior including resting pain, hyperalgesia, movement-evoked pain or anxiety- and depression-like behaviors after surgery. Furthermore, the role of certain receptors, mediators, and neurotransmitters involved in peripheral and central sensitization after incision were identified; many of these are very specific, relate to some modalities only, and are unique for incisional pain. Future treatment should focus on these targets to develop therapeutic agents that are effective for the treatment of postoperative pain as well as have few side effects. Furthermore, basic science findings translate well into results from clinical studies. Scientific evidence is able to point towards useful (and less useful) elements of multimodal analgesia able to reduce opioid consumption, improve pain management, and enhance recovery.

Conclusion: Understanding basic mechanisms of postoperative pain to identify effective treatment strategies may improve patients' outcome after surgery.

Keywords: Ketamine; Multimodal analgesia; Postoperative pain; Pregabalin; Sensitization; Surgical incision.

Conflict of interest statement

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Figures

Figure 1.
Figure 1.
Postoperative pain is associated with increased trafficking of the GluR1 subunit of AMPA-receptors by phosphorylation of Ser-831. Surgical plantar incision enhances the membrane translocation of PKCγ, but not other PKC isoforms, and induces the phosphorylation the Ser-831 site of the GluR1 subunit from AMPA-receptors. Stargazin interacts with the phosphorylated subunit in the endoplasmic reticulum compartment and trafficking into the neuronal membrane., The enhanced phosphorylation of GluR1 subunit and interaction of stargazin increased insertion of Ca2+ -permeable AMAPA receptors in the postsynaptic density (via PSD-95) that enhanced spinal nociceptive transmission. AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; Ca, calcium; CaMKII, Ca2+/calmodulin-dependent protein; DAG, diacylglycerin kinase II; ERK, extracellular-signal Regulated Kinase; GluR, AMPA receptor subunit; GPCR´s, G-Protein-coupled recetors; IP3, inosit-1,4,5-trisphosphat; MEK, mitogen-activated protein kinase kinase; P, phosphat; PKA, phospho kinase A; PKCγphospho kinase C gamma; PLC, phospholipase C; PSD-95, postsynaptic density-95; Ser, serine.
Figure 2.
Figure 2.
Epigenetic mechanisms modulate nociceptive sensitization after incision. Intra plantar (i.pl.) application of DNA-methyltransferase (DNMT) inhibitor (5-Aza-2´-deoxycytindine) reduced DNA-methylation and attenuated mechanical/heat hyperalgesia (↓), paw thickness (↓), and reinforced peripheral µ-opioid receptor mRNA expression (↑). The inhibition of Histon-deacetylase (HDAC) with suberoylanilide hydroxamic acid (SAHA, i.p.) reinforced mechanical hyperalgesia (↑). However, treatment of histon acetyltransferase inhibitor anacardic acid (ACA, i.p.) attenuated mechanical hyperalgesia (↓).

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