# Recovery of Post-Traumatic Temporomandibular Joint after
## 3 Rehabilitation of TMJ
### Non-Surgical Treatment  
#### 3.1.1 Pharmacotherapy  
The goal of pharmacotherapy is to relieve the symptoms and is a component of a comprehensive management program. The pharmacotherapy includes analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), anxiolytics, anti-depressants, and muscle relaxants [8; 27; 28; 29]. Non-steroidal Anti-inflammatory Drugs. Non-steroidal anti-inflammatory drugs (NSAIDs) are medicines commonly prescribed for the treatment of minor-to-moderate pain, fever, and other inflammatory processes given their antipyretic, analgesic, and anti-inflammatory activities [30; 31; 32; 33; 34]. The key mechanism of action of NSAIDs remains the inhibition of the enzyme cyclooxygenase (COX), particularly the COX-2 isoenzyme. In fact, there are two main COX isoforms with specific functions involved either in normal functioning and protection (COX-1) or in the generation of prostaglandins responsible for pain and inflammation (COX-2). Although typically found in all tissues and cell types, COX-1 isoenzyme is concentrated in several tissues and internal organs including stomach, kidney, endothelium, and platelets. COX-1 is a molecule that supports the synthesis of prostaglandins and is involved in platelet aggregation, the regulation of kidney and stomach blood flow, and the regulation of gastric acid secretion. The inhibition of COX-1 activity due to the effects of NSAIDs can induce gastrointestinal toxicity, cardiovascular and renal events, or delayed blood coagulation. On the other hand, the COX-2 isoenzyme is widely induced by inflammatory triggers and/or trauma; it is located in macrophages, leukocytes, fibroblasts, and synovial cells. Considered an inducible isoenzyme, COX-2 plays a key role in pain and inflammatory processes [31; 32; 33; 34; 35; 36; 37], and by blocking COX-2, NSAIDs can exert their analgesic effects. However, there is a constitutive COX-2 involved in the physiology of pregnancy. According to their selectivity for one or other of COX isoenzymes, NSAIDs are classified in (i) _classical, non-selective NSAIDs_, known to inhibit both COX-1 and COX-2 enzymes with the same potency and thought to have benefits in reducing pain and inflammation doubled by a typical side-effect profile; and (ii) _oxis or selective NSAIDs_ resulting only in COX-2 inhibition at therapeutical doses, with remarkable analgesic effects and also a favorable gastrointestinal profile with no impact on gastrointestinal safety. _Preferential COX-2 inhibitors_ represent an intermediate class of NSAIDs, quite recently described, that include NSAIDs which inhibit preferentially COX-2 at therapeutic doses and have potent analgesic and anti-inflammatory activity and only small negative influences on COX-1 enzyme; we discuss nimesulide, meloxicam, and nabumetone. _Specific COX-2 inhibitors_ or _coxis_ are represented by three main agents-celecoxib, etoricoxib and the intravenous parecoxib; the coxib on market, rofecoxib, was discontinued due to cardiovascular safety [30; 31; 32; 33]. The usual doses of different NSAIDs are summarized in Table 1.  
There are several possible adverse effects of taking NSAIDs, especially with non-selective NSAIDs, which may occur at any time throughout the whole treatment period. The most commonly described are as follows: gastrointestinal, cardiovascular, complications, impaired renal function, clotting problems as well as respiratory disorders. Apart from an improved gastrointestinal safety, coxis hold comparable side-effects profile with classical NSAIDs [30; 31; 32; 33]. To achieve an anti-inflammatory effect in TMDs, these medications should be taken for a minimum of 2 weeks. Naproxen and ibuprofen are recommended first-line choices NSAIDs in patients with cardiovascular comorbidities, due to the lower risk of cardiovascular, while coxis are preferred when gastrointestinal comorbidities [30; 31; 32; 33].