**4.1 Musculoskeletal pain (MP)**

Given the multiplicity of mechanisms responsible for MP, the combination of analgesics with different mechanisms of action for the relief of acute and chronic skeletal muscle pain is often recommended, with the possible advantage of pharmacokinetic synergy and improved patient adherence.

The main pharmacological associations currently available for the treatment of MP are [19]:


For all these combinations, careful monitoring must be performed in order to assess whether continuation of therapy, suspension, or transition to a strong opioid is necessary [19].

#### **4.2 Osteoarthritis (OA) pain**

Pain associated with rheumatologic conditions has a strong peripheral nociceptive component, although recent data also suggest a central sensitization [37]. Ideal treatment of rheumatic pain should be through a multimodal approach, integrating non-pharmacologic and pharmacologic treatments [38]. In the context of rheumatological painful conditions, the association of dexketoprofen and tramadol may represent an attractive medication for acute exacerbations of OA pain, due to its pharmacological profile: the combination of dexketoprofen and tramadol, targeting different sites of action, is suitable for OA type of pain, arising from different body structures (joints, muscles, ligaments, etc.) [21]. The rapid onset of analgesic effect of dexketoprofen, with its anti-inflammatory activity, associated to the sustained action of tramadol, makes their combination a valuable tool to achieve multimodal analgesia in OA patients [21].

#### **4.3 Back pain**

Back problems are the third reason for seeking medical help, with about 90% of people suffering from them at some point in their lives [39, 40]. Most episodes of back pain are short lasting with little or no consequence, but recurrent episodes are common and back pain is increasingly understood as a long-lasting condition with a variable course rather than episodes of unrelated occurrences [41]. The complexity of chronic back pain management highlights the need for early intervention in patients with acute back pain in order to prevent progression to chronic back pain [42]. Chronic low back pain has been shown to be secondary to both neuropathic and nociceptive pain mechanisms [43]: a multimodal approach is therefore appropriate. The pain treatment armamentarium for both acute and chronic back pain includes NSAIDs, opioids, steroids, topical medicines, and adjuvants: the choice of medication depends on a number of factors, including the duration of symptoms, severity of symptoms, expected benefits, prior response to medications, adverse effect profile, presence of comorbidities, costs, and degree of supporting evidence [44]. Most guidelines endorse (NSAIDs) and weak opioids for short periods when there is contraindication or lack of improvement with NSAIDs [45].

**209**

*Multimodal Pharmacological Analgesia in Pain Management*

Fibromyalgia is mainly a centralized pain disorder, accompanied by fatigue, sleep disturbance, and memory and mood difficulties [43]. Effective drugs combinations for this condition include tramadol + paracetamol [46], cyclobenzaprine + fluoxetine [47], pregabalin added to either quetiapine or trazodone [48], and

Surgical pain may be nociceptive, neuropathic, mixed, psychogenic, or idiopathic, depending on the surgical procedure. The value of balanced analgesia in treating postoperative pain was recognized by Kehlet and Dahl [9] over two decades ago. Non-opioid analgesics are the cornerstone of postsurgical pain multimodal management: in addition to their opioid-sparing effects, many of these agents are highly effective in reducing postoperative pain and allowing for faster mobilization [50].

• Many current multimodal protocols include paracetamol [51–53], based on its opioid-sparing effects, despite the risk of GI, CV, and hepatic adverse

• NSAIDs represent another class of medication that is highly effective for perioperative pain management: despite concerns about the increased risk of postoperative bleeding with NSAIDs, a meta-analysis revealed that ketorolac does not increase the risk of perioperative bleeding [54]. Nevertheless, this drug has shown several other side effects. Preoperative COX inhibitors (primarily selective COX-2 inhibitors) [55] and postoperative nonselective and selective NSAIDs [56] have been associated with reduced postoperative opioid consumption [57]. The combination of NSAIDs with opioids represents another tool to limit opioid use: in particular, the combination dexketoprofen/ tramadol was shown to be superior vs. single components in terms of control of moderate-to-severe acute pain after abdominal hysterectomy [58] and total hip arthroplasty [59], with a safety profile fully in line with that previously known for the single agents in monotherapy. Recently, the analgesic efficacy of dexketoprofen/tramadol was compared in a head-to-head study (DAVID study) to that of tramadol/paracetamol combination in moderate-to-severe pain following surgical removal of impacted lower third molar, showing the

greatest sustained analgesia during the 6-hour post dose period [60].

sedation, particularly in elderly patients.

function and decreases postoperative morbidity [66].

• Another class of analgesics commonly used in multimodal analgesic protocols is the gabapentinoids, which include gabapentin and pregabalin. Meta-analyses have demonstrated that gabapentin [61] and pregabalin [62] improve postoperative pain when part of a multimodal regimen but are associated with

• Other agents to consider in multimodal protocols include NMDA antagonists, such as ketamine. Ketamine has a clear opioid-sparing effect in the perioperative period [63] and may reduce long-term opioid consumption in opioid-tolerant patients [64] as well as persistent postsurgical pain when used intravenously [65].

• Multimodal and preemptive analgesia as part of an ERAS (Enhanced Recovery after Surgery) protocol facilitates early mobility and early return of bowel

*DOI: http://dx.doi.org/10.5772/intechopen.93620*

fluoxetine + amitriptyline [49].

**4.5 Postsurgical pain**

events [25, 26].

**4.4 Fibromyalgia**
