The inroads made over the last decade have greatly increased our knowledge in pain conduction and perception. This has lead to pain management protocols that place excellent pain control modalities in the hands of the clinician. Trigeminal anatomy, the physiology of pain and the anatomical basis for pain management protocols are described. Concepts of pre-emptive analgesia, catastrophization of pain, and convergence are reviewed and integrated into the clinical practice setting. The introductions of the multi-modal approach along with a thorough anatomic description of the pathways that facilitate this approach are described. This article should leave the astute clinician with the armamentarium to treat the vast majority of clinical pain presentations.
The dental profession, since its infancy, has been a pioneer in the fields of anaesthesia and pain control. This stems from the need for these modalities in order to render pain free dental care in an anatomic region that is highly innervated by the second and third divisions of the trigeminal nerve. Pain has a dramatic physiologic impact that can adversely affect the health and well being of dental patients. Pain can have a profound effect on the cardiovascular, pulmonary, endocrine and gastrointestinal systems. Furthermore, if acute pain is not treated adequately, there is a risk that it may become chronic in nature. Therefore adequate pain control is a medical and dental necessity and not merely an issue of patient comfort.
The International Association for the Study of Pain has promoted the following definition; “Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms as such damage”. Acute pain is described as a psychological and autonomic physiologic response to an adverse chemical, thermal, or mechanical stimulus such as surgery. Acute pain, which is primarily caused by tissue damage such as a dental extraction, usually lasts from minutes to weeks, is self-limiting, and should resolve with the resolution of cause.1 Post-surgical pain is best described as ‘acute nociceptive pain’ since the sensation of pain is transmitted by specific pain receptors called nociceptors. This article reviews effective post-surgical pain management for the dental practitioner.
Pain mediators such as bradykinin, cytokines and serotonin (5-hydroxytryptamine, 5-HT) are specific chemicals that stimulate nociceptors, and are released at the site of tissue damage.1 These nerve endings are further sensitized by prostaglandins, which can contribute to the pain experience considerably. The combination of mediators and prostaglandins at the site of tissue trauma is sometimes referred to as “inflammatory soup” (Figure 1). These chemical mediators are an extremely important component of the pain experience, as they constitute the initiation of the pain cascade. As such, it’s inhibition or suppression could have a significant effect on limiting the pain experience.
Once the pain receptors called nociceptors are stimulated, A-Delta and C nerve fibers conduct the signal to the spinal cord where the nerves synapse in the dorsal root, again in the thalamus and finally within the cerebral cortex (Figure 1). Each synapse contains one of the following neurotransmitters: nor-epinephrine, acetylcholine, or serotonin (Figure 1). In addition, there is a “descending anti-nociceptive tract” (DANT), which exerts an inhibitory effect on the transmission of the pain signal through its influence within the dorsal root of the spinal cord (Figure 2).
Pain signals originating in the orofacial region are carried through the trigeminal (gasserian) ganglion on to the trigeminal spinal tract where they then synapse within the subnucleus caudalis (Figure 3). The subnucleus caudalis (SC), which exhibits functional and morphologic similarities to the spinal cord dorsal horn, relays the signals to the thalamus where they synapse again and move on to higher cortical centres.2 Nociceptive neurons of the subnucleus caudalis converge from the tooth pulp, temporomandiblular joints, and muscles of mastication, oral cavity, and facial skin. This access of multiple afferent inputs onto a neuron is known as convergence. Convergence is believed to be one of the reasons responsible for the extensive degree of pain referral seen within the orofacial region.3
While trigeminal system pain has not been studied nearly as extensively as spinal cord mediated pain, it is believed that the mechanisms of pain modulation and conduction pathways are very similar.2
The extensive number of mediators, pathways and neurotransmitters that constitute the pain pathways permit multiple opportunities to block or prevent pain signals from reaching the cerebral cortex. Pain can be blocked at four different sites: at the site of tissue injury (peripherally); at the afferent nerves and nerve roots within the soft tissues (peripherally); within the spinal cord (centrally); within the higher cortical centers (centrally). (Figure 2)
At the site of tissue injury (peripherally), inflammation and its mediators, are the primary source of pain. Since prostaglandins sensitize the peripheral nociceptors, their inhibition can dramatically decrease the receptor stimulation and pain signal conduction. Non-steroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen exert their primary effects at this site (Figure 2).
Local anaesthetics can block afferent nerves and nerve roots within the soft tissues. (Figure 2). Generally, with acute tissue trauma mediated pain, no pain signal transmission to the cerebral cortex results in no perception of pain. In addition, nociceptor stimulation precipitates a complex cascade of events that includes the release of neurotransmitters centrally at multiple synapses. This dynamic response to pain stimulation is aborted by the use of peripheral local anaesthetic nerve blockade.
Within the spinal cord, opioid drugs such as morphine and codeine produce analgesia by acting at several levels within the central nervous system. These include the inhibition of neurotransmitter release within the spinal cord and activation of descending inhibitory controls (DANT) in the midbrain. (Figure 2) The notable analgesic potency of opioids is related to their influence at multiple sites along the central pain transmission pathways.
Within the higher cortical centers, both acetaminophen and NSAIDS exert a cortical pain inhibitory effect (Figure 4). This effect is exemplified by the centrally mediated anti-pyretic effect exhibited by both drugs. NSAIDS therefore produce analgesia both through peripheral and central effects while acetaminophen acts centrally alone. This explains the greater analgesic potency of the NSAID class of drugs.
It is now readily apparent that pain control should involve a multi-modal approach much like that used in the management of many medical disorders such as hypertension and ischemic heart disease.4 Pain management protocols can therefore take advantage of the various central and peripheral pain pathways that provide many opportunities to block or modify pain transmission. Multimodal therapy indicates the simultaneous use of drugs from different categories that act synergistically for a more effective outcome.4
Local anaesthetics block all pain signals p
eripherally which results in little or no pain signal conduction to the cerebral cortex (Figure 2). While the dental profession primarily uses local anaesthetics to produce anesthesia in order to facilitate pain-free dental and surgical procedures, they are also used in the management of chronic pain conditions. In addition, there appears to be a role for local anaesthetics in the provision of postoperative analgesia. Trieger et al in 1979 first demonstrated the post anaesthesia analgesia effect of bupivicaine when compared with carbocaine.5 Gordon et al compared lidocaine and bupivicaine in a third molar surgery pain model.6 They determined that patients who received 0.5% bupivicaine at the time of third molar surgery experienced significantly less pain 48 hours postoperatively. Unlike lidocaine and other amide local anaesthetics, bupivicaine appears to have an analgesic effect that far outlasts the period of anaesthesia. The results of this study imply the importance of blocking pain signals in the immediate post-operative period and not just intra-operatively. In this manner, the local anaesthetic bupivicaine acts in the form of a potent postoperative analgesic. This may be due to the prevention of the release of neurotransmitters centrally at multiple synapses. It is the prevention of this dynamic response to pain stimulation that makes peripheral local anaesthetic nerve blockades an effective pain control modality. It is important to note that bupivicaine exhibits this property only when used as a nerve block and not when used as an infiltration.
NSAIDS (e.g. ibuprofen, naproxen, acetylsalicylic acid or ASA) act to inhibit prostaglandin synthesis peripherally within the wound and centrally as they exhibit an inhibitory effect at the spinal dorsal root horn as well as an analgesic effect within the brain (Figures 5 & 6). The antipyretic properties of NSAIDS further confirm their centrally mediated affects. Their primary anti-inflammatory properties have lead to their classification as non-steroidal anti-inflammatory drugs. The NSAIDS can be broadly divided into two categories, non-selective cyclo-oxygenase (Cox) enzyme -1,2 inhibitors and selective Cox-2 enzyme inhibitors. The non-selective group is further subdivided based on its derivative compounds.
Cox-1,2 non-selective inhibitor NSAIDS include ibuprofen, naproxen, ketorolac and ASA. Prostaglandin I2 (PGI2), prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) are all inhibited by this class of NSAID. Their potential side effects which include GI upset, gastric bleeding, nausea, vomiting, anti-platelet effect, hypertension and renal failure are related to the inhibition of prostaglandins within the gastrointestinal tract (PGI2 and PGE2), kidneys (PGE2) and platelets (TXA2). An increase in their anti-inflammatory potency, length of use and increased dose can increase the incidence of adverse effects. The anti-platelet effect is drug dependent within this category. ASA exhibits profound irreversible anti-platelet effects while ibuprofen exhibits much lower effects that are essentially gone within twenty-fours of drug cessation.
COX-2 selective inhibitors, which include celecoxib (Celebrex®Pfizer), meloxicam (Mobicox®Boehringer-Ingelheim) and rofecoxib (Vioxx® Merck), gained rapid approval due to their purported improved side-effect profile when compared with non-selective COX inhibitors. They exhibit no anti-platelet effect, lower incidence of GI upset and a decrease in negative renal effects. This class of drugs reduces the risk of severe GI adverse effects such as ulceration or bleeding by one-third when compared with non-selective Cox inhibitors.7 COX-2 inhibitors recently received much attention with the removal from market of refoxicib (Vioxx®Merck), and valdecoxib (Bextra® GD Searle) due to their implication in an increased incidence of cardiac related deaths with long-term use.
Gordon et al tested post-operative prostaglandin levels for PGE2 and TXB2 within dental extraction sites.8 There was a strong positive correlation between prostaglandin tissue levels and reported onset of pain. In addition, prostaglandin tissue levels and recorded pain levels decreased in response to ketorolac. Ong et al demonstrated that pre-treatment with the NSAID ketorolac resulted in less post-operative pain in the third molar surgery pain model.9 The authors of the study concluded that the pre-emptive administration of NSAIDs may offer improved post-surgical pain control. A large meta-analysis study of 2246 patients in 22 clinical trials using selective Cox-2 inhibitors such as celecoxib for postoperative pain control found that there was a clear benefit in terms of reduced pain, reduced narcotic analgesic consumption and improved patient satisfaction10.
There is a clear role for NSAIDS in the management of post-surgical pain and it appears that timely early administration is key to achieving the maximum therapeutic benefit. While ibuprofen seems to have one of the best side-effect profiles, it is also relatively low in potency and requires high doses to match the analgesic potency of other NSAIDS such ketorolac and naproxen. Short-term administration of NSAIDS, as in the management of acute post-surgical pain, tends to minimize the incidence of side effects.
Acetaminophen, through its inhibition of central prostaglandin synthetase, possesses notable pain reduction properties that are only centrally mediated since it does not exhibit anti-inflammatory properties. (Figure 4). Side effects for this drug are truly minimal. Excessive doses can cause liver failure. Caution is warranted in patients with known liver impairment, alcoholism, or known hypersensitivity to acetaminophen.
Opioids (eg. codeine, morphine) provide pain relief by acting at several levels within the central nervous system (Figure 2). The predominant mechanisms by which opioids produce their analgesic effects is through the inhibition of neurotransmitter release in the spinal cord and by activation of descending inhibitory controls (DANT) morphine acts on ‘mu’ receptors, which inhibit the release of several neurotransmitters including nor-epinephrine, acetylcholine and the neuropeptide substance P. Morphine also stimulates the descending anti-nociceptive tract (DANT), which moderates the sensation of pain (Figure 2). The opioids are notable for their profound influence on pain mediation due to their diverse influence on the pain pathways. The side-effect profile of opioids includes nausea, vomiting, sedation, dizziness, drowsiness, dysphoria, respiratory depression as well as physical dependence, addiction and drug tolerance with long-term use.
In a study by Pavlin et al, it was found that catastrophizing, which is “an exaggerated mental set brought to bear during actual or anticipated painful experience”, was positively correlated with the experience of early post-surgical pain intensity11. Therefore the more a patient fears and anticipates pain, the more pain they are likely to perceive.
Anxiolytic drugs are indicated when pain is accompanied by anxiety, panic attack, catastrophization or “morbid fear”, insomnia and myospasm. The benzodiazepines (eg diazepam, lorazepam) are commonly known members of the psychotropic drug class. On a short-term basis, they improve sleep quality, attenuate bruxism, and relieve myospasm. This results in an elevation of the pain threshold and less overall muscle sourced pain. Psychotropic medications can play a very effective ancillary role in the management of post-surgical pain.
The anticipation of post-surgical pain should therefore result in the implementation of a protocol that incorporates a customized approach based on the needs of the individual patient. The concepts of multimodal therapy and maximum analgesic dosage are presented. The recommended medications and dosages in this article are typical for a healthy 70-kilogram adult. Medication and dosage adjustments should be made at the discretion of the practitioner based on the patient’s health status, medications, age, allergy profile and body weight.
In the quest to achieve adequate post-surgical analgesia, an inadequate dosage is a frequent cause for insufficient pain control. Use of the maximum therapeutic dose for a medication will ensure that the full analgesic potential of the drug is realized. In a healthy adult, 1000mg of acetaminophen can be given every 6 hours to a maximum of 4 grams per 24 hour period to manage mild pain.
In the family of NSAIDS, 600mg of ibuprofen can be given every 4-6 hours to a maximum of 2400mg. per 24-hour period. This can be substituted with naproxen 250-500mg. BID or the Cox-II inhibitor, celecoxib 200 mg. BID or ketorolac 10mg Q6H. Ketorolac must not be prescribed for more than 5 days due to its’ high incidence of GI side-effects. The GI side effects of short-term NSAID administration are best managed with a change to a different NSAID. H2 blockers such as ranitidine or famotidine, and antacids may offer some relief but misoprostol or proton pump inhibitors such omeprazole (Losec®Astra Zeneca) or esomeprazole (Nexium® AstraZeneca) have proven efficacy in decreasing the GI side effect incidence. Only one NSAID should be administered at a time.
The co-administration of one of the above NSAIDS with acetaminophen 1000mg q6h is an effective combination for mild to moderate pain control. Several pain pathways that include both central and peripheral effects are influenced by this combination.(Figure 5)
Again, the foundation of treatment should be a high dose NSAID such as ibuprofen 600mg q4-6h and pre-emptive analgesia such as a bupivicaine block when indicated. When moderate to severe pain is anticipated, narcotics should be utilized due to their strong analgesic properties. 30 mg of codeine is not better than placebo which implies that a typical adult dose should be 60 mg of codeine every 4-6 hours. Unfortunately, the typical side-effects associated with narcotics are often dose dependent. When used as a sole agent, the side-effects of codeine are often more profound than the analgesic effect.12 McQuay et al demonstrated that about 50% of patients taking codeine alone post third molar surgery required a change in their analgesic regimen either due to inadequate pain control or excessive side effects.12 This makes codeine a poor choice as a sole agent. Codeine, is therefore most often combined as a compound with other analgesic agents such as acetaminophen or ASA unless it is being used solely for its anti-tussive properties. Two Tylenol #3 ®(McNeil) tabs q4h provides a maximum codeine dose (60mg) but under-doses the acetaminophen component (600mg). Since codeine is not a potent narcotic, this compound often does not provide adequate analgesia in cases of moderate to severe pain.
The analgesia derived from compounds containing only 15mg of codeine per tablet such as Tylenol #2®(McNeil) should not be utilized for moderate to severe pain. Three Tylenol #2®(McNeil) tablets would provide close to the maximum dose of acetaminophen, 900mg. But only 45mg of codeine. It should also be noted that acetaminophen-codeine compounds also contain 15mg of caffeine per tablet, which can adversely affect sleep. Pentazocine 50-100mg every 3-4 hours to a maximum of 600mg per 24 hours is an effective narcotic analgesic regimen that is best combined with acetaminophen 1000mg q6h and an NSAID such as ibuprofen 600mg q4h.
Due to the combined agonist-antagonist properties of pentazocine, it is best avoided in patients that currently use narcotics routinely.
For narcotic induced nausea, dimenhydrinate 50mg taken every 6 hours or metaclopramide 10mg every 6 hours or odansetron 8mg every 6-8 hours may be beneficial. Severe nausea and or vomiting should lead the clinician to change the drug regimen either to exclude the narcotic family completely or trial a different narcotic-like medication such as Tramacet® (Janssen-Ortho) that fewer side-effects.
For severe pain, a multimodal approach is indicated which should include acetaminophen, ibuprofen 600mg q6h and a potent narcotic. Percocet®Endo which contains oxycodone 5mg and acetaminophen 325mg per tablet is indicated at a dose of 2 tablets q4-6h for severe pain despite the fact that it too under-doses the acetaminophen component when 2 tablets are taken. The treatment course should be limited due its street desirability and addictive properties. Tramacet® (Janssen-Ortho), a new analgesic to Canada, which contains tramadol 37.5mg (a narcotic-like medication) and acetaminophen 325mg, is also a good choice in this category.13 The side effect incidence of tramadol is considerably lower than for most narcotics.
Whenever a patient presents with pain that is well beyond reasonable expectations it should alert the astute practitioner to search for other contributing factors, such secondary gain issues, drug addiction, underlying myofascial pain syndrome, dry socket and alternate pain sources such as referred pain syndromes. This is where psychotropic drugs can play a significant role in pain management. Long-term high dose narcotics should not play role in the management of acute pain conditions of odontogenic origin. A protocol for severe pain should include a maximum dose of NSAID such ibuprofen 600mg q4-6h along with a potent narcotic oxycodone- acetaminophen combination such as Percocet®(Endo), 2 tabs q4-6h. Mandibular block anaesthesia should be rendered with the local anaesthetic bupivicaine due to its post-anaesthetic analgesic properties. This modality can be used in the postoperative period as well. Consideration could also be given to using an anxiolytic such as diazepam 5-10mg. or lorazepam 1mg. q6h when anxiety or myofascial pain due to parafunction is present. This pain management protocol addresses at least four pathways and adheres to the maximum analgesic dose concept. Caution is always advised when medications that cause sedation such as narcotics and benzodiazepines are given simultaneously. In cases when moderate to severe pain is anticipated, round the clock dosing may offer better pain control than administration on a prn basis. It is better to prevent pain than to play catch-up. To this end, providing an analgesic, especially the NSAID, either immediately before or shortly after surgery and then as round the clock dosing is notably beneficial.
Several recent studies have examined the analgesic properties of gabapentin in the post-surgical pain scenario. Gabapentin is now commonly used for the treatment of epilepsy and chronic pain conditions such as post-herpetic or trigeminal neuralgia. Its mechanism of action is unknown although it is believed to be centrally acting. Pandey et al. 13 found that 300 mg gabapentin administered two hours pre-operatively was effective at reducing pain 24 hours post-operatively and higher doses were not necessary. Gilron et al. 14 found that simultaneous administration of gabapentin and rofecoxib two hours pre-operatively and 24 hours post-operatively offered improved pain control. Gabap
entin may also exhibit anxiolytic properties that would only enhance its analgesic potential15. Similar analgesic benefits have been found with the preoperative use of Pregabalin16. The benefits of gabapentin as an adjunct for neurolept anaesthsia have been demonstrated as well.17 It is likely that the use of gabapentin or pregabalin alone or in combination with an NSAID will become common practice in the pre-emptive management of post-surgical pain.
Pain protocols should be tailored to the anticipated requirements of individual patients.
1. Pain management approaches that involve multiple pain pathways through the utilization of a multimodal approach are more likely to provide adequate analgesia.
2. The use of bupivicaine for mandibular block anaesthesia is a simple pre-emptive technique with proven efficacy.
3. The administration of maximum analgesic doses of medications with low side-effect profiles will also ensure improved pain control.
4. The recognition of potential catastrophization or emotional factors should lead to the use of psychotropic agents as adjuncts in pain management.
5. Round the clock dosing will contribute to the prevention of pain, which is much, more effective than playing “catch-up” once pain has set in.
The institution of protocols that adhere to these principles should facilitate excellent pain management under most conditions. The introduction of well-planned pain management protocols will ensure optimum patient satisfaction, minimize the medical sequella of pain and prevent the potential establishment of long-term pain syndromes. OH
Dr. Frydman is a Clinical Associate Professor of Surgery University of Illinois, an Adjunct Clinical Professor Division of Orthodontics, University of Western Ontario; Chief of Surgery and VP Medical staff at St. Thomas Elgin General Hospital and is a Diplomat of the American Board of Oral and Maxillofacial Surgery. Dr. Frydman is a partner at the Private Practice Interface Centre for Oral & Maxillofacial Surgery in London, ON, Canada.
Dr. Frydman can be contacted at: wfrydman@uwo.ca
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