Does previous drug use cause a level of tolerance to local anesthetics?

Question: “I have a patient with history of cocaine and heroin addiction, but has been clean for 5 years.  It seems that local anesthetic (lidocaine 2%, 1:100k epi) for minor restorative wears off sooner than I would normally expect. Would her previous drug use cause a level of tolerance to the local anesthetics?”

Dr. Joonyoung Ji provided the below answer. He is resident in the Department of Dental Anesthesia at the University of Toronto

What is pain?

Under the International Association for the Study of Pain, “Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”. Thus, pain is both physical and emotional and personalized to each individual. It is important to note that the experience of pain is not necessarily related to the degree of tissue damage. An example would be a patient with allodynia; a normally non-painful stimulus causing pain, or hyperalgesia; an exaggerated pain response to a stimulus.

Pain transmission is not hardwired, it exhibits neuronal plasticity. This means that perception of pain changes as painful stimuli is repeated. For example, untreated acute pain causes pain pathways in the CNS to alter so that it changes to a state of chronic pain, a process called central sensitization.

What are the psychotropic effects of cocaine?

Cocaine releases and blocks the re-uptake of neurotransmitters norepinephrine, epinephrine, and dopamine. The pleasurable effects are described as euphoria and CNS stimulation. They are manifested as; elation, arousal, alertness, greater sensory awareness, lack of fatigue and appetite. However, there are major dysphoric aspects to cocaine as well. These are anxiety, agitation, paranoia, psychosis, panic-attacks, potentiation of fear and anxiety. (1, 2). To mitigate the dysphoric aspects of cocaine, alcohol and benzodiazepines, both CNS depressants, are often used in conjunction. (3, 4)

What are the physiological effects of cocaine?

Cocaine inhibits the uptake of norepinephrine by premotor neurons and thus to potentiate neurogenic vasoconstriction. The major risk of cocaine physiologically is the cardiovascular and central nervous system. Neurologic symptoms range from visual blurriness, headache, dizziness, sensory and motor abnormalities to generalized tonic-clonic seizures, loss of consciousness, and coma. Cardiovascular wise, it causes tachycardia while constricting coronary vessels and systemic hypertension. The individual is prone to myocardial ischemia, aneurysms, strokes, and ruptured vessels. (2) Anecdotally, very commonly, a young patient in their 20’s or 30’s presenting to emergency receiving a diagnosis of heart attack has been abusing cocaine.

What are the psychotropic effects of heroine?

The abuser experiences a feeling of warmth followed by alternating periods of high energy and sedation. After the initial sensation of euphoria, typical opioid effects such as decreased mental alertness, and increased sedation, and possibly somnolence. Heroine causes anxiolysis and users describe a feeling of contentment.

What are the physiological effects of heroine?

Heroine produces effects typical of an opioid. These are sedation, miosis, pruritis, decreased cellular immunity, analgesia, constipation, and respiratory depression. Most reported cases of death are due to respiratory depression.

Mechanism of local anesthesia

Local anesthetics block voltage-gated Na channels along the axonal membrane, preventing nerve depolarization. A sufficient concentration at the site of action to block at least 3 nodes of ranvier are typically needed for successful local anesthesia in dentistry. As the deposit of local anesthetic gradually decreases via absorption by the circulating vasculature, recovery from local anesthesia is seen.

What are the possible reasons for this observation?

A scientific theory as to why recreational drug use is associated with recalcitrant local anesthesia remains to be seen.

Cocaine is a potent CNS stimulant that potentiates fear and anxiety. Both of which can alter the experience of pain. (5) Cocaine users also exhibit heightened defensive behaviors and are predisposed to increased sympathetic reactions.

Heroin is an opioid to which tolerance quickly develops and is a natural physiologic response to constant opioid receptor stimulation. Opioid receptors are located in the pain pathways in the spinal cord.

Difficulty with local anesthesia for recreational drug users is casually observed in clinical practice and in literature. (6) It is paradoxical that cocaine, a substance that causes vasoconstriction and is a local anesthetic itself, is associated with difficulty achieving local anesthesia. This patient might have been using heroin, a depressant and analgesic, to mitigate the unwanted effects of cocaine.

Pharmacodynamic factors in local anesthesia include the effects on both peripheral sensitization of nerves and central sensitization. Past and current recreational drug use might be altering the emotional perception of pain, i.e. they might be normalizing to a new “set-point”.

It has been shown that anxiety and fear has a pain-increasing effect. (7) One could hypothesize that since many recreational drugs produce these dysphoric states of mind, these patients may be in a state of hyperalgesia. 

Clinical implications

Current and past recreational drug users are associated with difficulty achieving local anesthesia. Although there are no current scientific understandings of this observation, expert opinion suggests that this group of patients may have an altered sensorium and have a lower pain threshold. Local anesthetics work at the site of injection, not systemically. Physiologic tolerance would not develop to local anesthetics. 

In managing this poorly understood observation, the best approach to patients who have a history of recreational drug abuse may have to be symptomatic.

1. Ensure profound local anesthesia by making use of alternate injection techniques in addition to the customary technique.
2. Employ anxiety decreasing measures such as sedation with a benzodiazepine for those dentists with appropriate training.
3. Patients should be instructed to continue physician prescribed drugs, especially if they are for treatment of withdraw or ongoing maintenance therapy.
4. Delay appointment if recent abuse is suspected. Recent cocaine use is a major cardiovascular risk and withdraw symptoms may last for weeks.
5. Long term psychiatric problems persist for months even years after last known abuse. (8)

References

1. Blanchard DC, Blanchard RJ. Cocaine potentiates defensive behaviors related to fear and anxiety. Neurosci Biobehav Rev 1999;23(7):981-91.
2. Lowenstein DH, Massa SM, Rowbotham MC, Collins SD, McKinney HE, Simon RP. Acute neurologic and psychiatric complications associated with cocaine abuse. Am J Med 1987;83(5):841-6.
3. Grant BF, Harford TC. Concurrent and simultaneous use of alcohol with cocaine: results of national survey. Drug Alcohol Depend 1990;25(1):97-104.
4. Sheehan MF, Sheehan DV, Torres A, Coppola A, Francis E. Snorting benzodiazepines. Am J Drug Alcohol Abuse 1991;17(4):457-68.
5. Klages U, Ulusoy O, Kianifard S, Wehrbein H. Dental trait anxiety and pain sensitivity as predictors of expected and experienced pain in stressful dental procedures. Eur J Oral Sci 2004;112(6):477-83.
6. Tamer A. Pain Threshold, C-Reactive Protein and Efficiency of Local Anesthesia in Addictive Drug Abusers with Impacted Lower Third Molar Tooth. 2012.
7. Brand HS, Gortzak RA, Palmer-Bouva CC, Abraham RE, Abraham-Inpijn L. Cardiovascular and neuroendocrine responses during acute stress induced by different types of dental treatment. Int Dent J 1995;45(1):45-8.
8. Kalant H. The pharmacology and toxicology of “ecstasy” (MDMA) and related drugs. CMAJ 2001;165(7):917-28.