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single agents [6, 7].

**Chapter 12**

**Abstract**

**1. Introduction**

Multimodal Pharmacological

*Antonella Paladini and Giustino Varrassi*

Analgesia in Pain Management

The knowledge of the pathophysiology of pain has gradually evolved in recent years, allowing the development of new management strategies, more specifically addressing single pain types and patient profiles. Despite these advancements, pain management still remains an open issue, given the limitations of single agent therapies, the potential abuse/misuse of opioids and the risk of adverse events. The advent of multimodal analgesic strategies paves the way for major improvements in pain management, combining increased efficacy with better tolerability and an opioid-sparing effect. The association of analgesics with different mechanisms of action represents a successful strategy for a wide range of pain conditions, minimizing side effects and taking advantage of the additive or synergistic actions of individual agents. Last but not least, the increasing availability of oral fixed-dose combinations of analgesics will offer further advantages over extemporaneous combinations, by increasing ease of administration and patient adherence to treatment.

**Keywords:** acute pain, chronic pain, analgesia, multimodal, drug combination,

Whatever its cause, pain, both acute and chronic, often emerges from multiple pathogenic pathways [1], which makes drug treatment particularly difficult [2]. In recent decades, the pharmacological arsenal against pain, in addition to traditional nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol, has been enriched, on the one hand with molecules operating on different pain mechanisms (as anticonvulsants and antidepressants), and on the other hand with opioids [3]. However, the single-agent approach to pain remains quite challenging, since a single drug, acting on a single pain component, is generally not successful to achieve a clinically meaningful pain reduction, whereas its use at high doses may cause significant side effects [2]. On the other hand, the increasing prescription of opioids for noncancer chronic pain, besides providing limited clinical advantage compared with non-opioid alternatives [4], has opened the door to problematic opioid use and addiction problems: up to 50% of patients on long-term opioid therapy develop physical dependence or tolerance, leading to problematic opioid use in 5–10% of patients and to addiction in 1–2% [5]. As a consequence, pain management is far from being optimal and patients are exposed to the risks associated with misuse of

opioid, anti-inflammatory agents, nonsteroidal, acetaminophen
