Table 3.
A selection of drugs commonly used in orofacial pain conditions in humans with examples of studies performed in animal models. The table lists examples of both positive and negative studies observed with presented drugs. No attempt was made to critically conclude based on the quality of the studies whether the drug indeed has pain-relieving efficacy. Where possible, reviews have been quoted which have compared various clinical studies and analyzed the drugs efficacy
| Type of drug | Specific name | Clinical use/results | Animal pain model1 | Behavioral test/s | Species | Efficacy/dosage and administration | |||
|---|---|---|---|---|---|---|---|---|---|
| Local anesthetics | Lidocaine (alphacaine) | TN – effective (Kanai et al. 2006), PHN – effective (Kanai et al. 2010) | Formalin | Face rubbing response observed | Rat | Yes (50 μL upper lip injection) (Dallel et al. 1995) | |||
| IoN-CCI | Von Frey | Rat | Yes (1, 2, and 4% solution; local injection into rostral orbital cavity) (Idanpaan-Heikkila and Guilbaud 1999) | ||||||
| Anti spasticity drugs | Baclofen | TN – effective (Watson 2004; Zakrzewska 2009) | IoN-CCI | Von Frey | Rat | Yes (3, 5, 10 mg/kg, i.p.) (Idanpaan-Heikkila and Guilbaud 1999) | |||
| Anticonvulsants (carboxamides) | Carbamazepine | TN – effective, second choice (Watson 2004; Zakrzewska 2009) | IoN-CCI | Von Frey | Rat | Yes (25–50 mg/kg i.p.) No (5–10 mg/kg, i.p.) (Idanpaan-Heikkila and Guilbaud 1999) | |||
| Trigeminal ganglion compression | Air puff | Yes (50 mg/kg i.p.) No (25 mg/kg i.p.) (Ahn et al. 2009b) | |||||||
| Oxcarbazepine | TN – effective (Zakrzewska 2009) | No animal studies in the trigeminal region | |||||||
| Anticonvulsants (GABA analogs) | Gabapentin | Poor results in TN (Watson 2004; Zakrzewska 2009) | IoN-CCI | Von Frey | Rat | Yes (100 mg/kg or 2 × 30 mg/kg or 2 × 50 mg/kg i.p.) No (30, 50 mg/kg i.p.) (Christensen et al. 2001) | |||
| MS-TN – some positive reports (Khan 1998; Solaro et al. 1998; Solaro and Messmer 2010) Effective-NP of head and neck (Sist et al. 1997), PHN (Lewis et al. 2007) | IoN-CCI | Air puff, von Frey | Mouse | Yes (2 × 30 mg/kg i.p.) (Krzyzanowska et al. 2011) | |||||
| Formalin | Face rubbing response observed | Rat | Yes (ED50 8.27 µg intrathecal) (Grabow and Dougherty 2002) | ||||||
| Pregabalin | TN and other neuropathic conditions – moderate results (Obermann et al. 2008; Navarro et al. 2011) | No animal studies in the trigeminal region | |||||||
| Anticonvulsants (benzodiazepines) | Clonazepam | BMS – effective (Zakrzewska et al. 2005) | No animal studies in the trigeminal region | ||||||
| Diazepam | TMD – effective (List et al. 2003; Zakrzewska 2010) | No animal studies in the trigeminal region | |||||||
| Anticonvulsants (others) | Lamotrigine | TN – effective – second choice (Zakrzewska 2009) or add-on (Watson 2004) | IoN-CCI | Von Frey | Rat | No (5–100 mg/kg i.p.) (Christensen et al. 1999) | |||
| Tricyclic antidepressants | Amitriptyline | Persistent facial pain and TMD (List et al. 2003; Zakrzewska 2010), PHN (Lewis et al. 2007) | IoN-CCI | Von Frey | Rat | No (0.5, 2, 10 mg/kg) (Idanpaan-Heikkila and Guilbaud 1999) | |||
| Formalin | Face rubbing response observed | Rat | Yes (ED50 value: 14.6 mg/kg s.c.) (Luccarini et al. 2004) | ||||||
| Clomipramine | TN – unknown efficacy (Zakrzewska 2010) | IoN-CCI | Von Frey | Rat | No (1.5, 6 mg/kg i.p.) (Idanpaan-Heikkila and Guilbaud 1999) | ||||
| Partial IoN ligation | Spontaneous face rubbing and rubbing after acetone application | Mouse | Yes (1.5 mg/kg) (Alvarez et al. 2011) | ||||||
| NMDA blockers | Ketamine | TMD – not effective (Castrillon et al. 2008) | Capsaicin | Face grooming response observed | Rat | Yes (0.4, 1.25, 4, 12.5 mg/kg s.c.); improved efficacy when combined with morphine (Alvarez et al. 2003) | |||
| Opioids | Morphine | Generally not used for neuropathic orofacial pain conditions in humans; some efficacy in PHN (Lewis et al. 2007) | IoN-CCI | Von Frey | Rat | No (1 mg/kg i.v.) (Idanpaan-Heikkila and Guilbaud 1999) | |||
| IoN-CCI | Von Frey | Rat | Yes (10 mg/kg i.p.) (Deseure et al. 2002) | ||||||
| Trigeminal ganglion compression | Air puff | Rat | Yes (2 or 5 mg/kg i.p. or 5 mg intracisternal) (Le et al. 2010) | ||||||
| TMD – intra-articular injections seem to be effective (List et al. 2001) | Mustard oil into TMJ | Jaw muscle response | Rat | Yes (15 nmol intra-articular) (Bakke et al. 1998) | |||||
| Formalin | Face rubbing response observed | Rat | Yes (5 mg/kg i.p.) (Clavelou et al. 1989) | ||||||
| Formalin | Face rubbing response observed | Mouse | Yes (ED50 value: 2.45 mg/kg s.c.) (Luccarini et al. 2006) | ||||||
| Capsaicin | Face grooming response observed | Rat | Yes (various doses of capsaicin and morphine tested; various administration methods) (Pelissier et al. 2002) | ||||||
| Capsaicin/glutamate | Face grooming response observed | Mouse | Yes (5 mg/kg i.p.) (Quintans-Junior et al. 2010) | ||||||
| Carrageenan | Operant behavior paradigm | Rat | Yes (0.5 mg/kg s.c.) (Neubert et al. 2005a) | ||||||
| CFA | Air puff, von Frey | Mouse | Yes (3 mg/kg i.p.) (Krzyzanowska et al. 2011) | ||||||
| NSAIDs2 | Acetylsalicylic acid | Commonly used although mostly for acute pain | Formalin | Face rubbing response observed | Rat | Yes (400 mg/kg i.p.) (Clavelou et al. 1989) | |||
| Indomethacin | Widespread use for migraines but little published data can be found for other orofacial disorders | CFA in skin, TMJ, and muscle | Spontaneous behavior and eating habits | Rat | Yes (4 mg/kg i.p.) (Thut et al. 2007) | ||||
| Carageenan | Face rubbing response observed | Rat | Yes (2.5 mg/kg) (Rodrigues et al. 2006) | ||||||
| CFA | Von Frey and thermal stimulation | Rat | Yes (5–10 mg/kg i.p.) (Morgan and Gebhart 2008) | ||||||
| Trigeminal ganglion compression | Air puff | Rat | Yes (25, 50, 100 μg/10 μL intracisternal) (Yang et al. 2009) | ||||||
| Dipyrone | Commonly used analgesic although withdrawn from most countries for side effects | Mustard oil in TMJ | Face rubbing response observed | Rat | Yes (19, 57, or 95 mg/kg i.v.) (Bonjardim et al. 2009) | ||||
| Diclofenac | TMJ osteoarthritis: effective (Mejersjö and Wenneberg 2008), not effective (Ekberg 1998) | Formalin | Face rubbing response observed | Rat | Yes – second phase only (10 and 30 mg/kg i.p.) (Padi et al. 2006) | ||||
| Naproxen | TMJ osteoarthritis: effective (Ta and Dionne 2004) | Formalin | Face rubbing response observed | Rat | Yes (ED50 value: 17 mg/kg i.p.) (Miranda et al. 2009) | ||||
| Other analgesics | Paracetamol | Commonly used although mostly for acute pain | Formalin | Face rubbing response observed | Rat | Yes (300 mg/kg i.p.) (Clavelou et al. 1989) | |||
| Formalin | Face rubbing response observed | Mouse | Yes (ED50 value: 100.66 mg/kg s.c.) (Luccarini et al. 2006) | ||||||
TN, trigeminal neuralgia; PHN, postherpetic neuralgia; CCI, constriction injury model; IoN, infraorbital nerve; TMD, temporomandibular disorders; MS, multiple sclerosis; NSAIDs, nonsteroidal antiinflammatory drugs; TMD, temporomandibular joint disorder.
1
In the inflammatory models, the inflammatory substance was injected into the skin unless otherwise indicated.
2
NSAIDs are often prescribed by dentists, general practitioners, and also specialists. However, few conclusive studies in humans have been performed on NSAIDS in TMD and other orofacial pain disorders. For systematic reviews see: Mujakperuo et al. (2010) and List et al. (2003).