Harry B Skinner
Professor and Chairman
Department of Orthopaedic Surgery
University of California
Irvine Medical Center
The most common reason a patient seeks the care of a doctor is the onset of pain of some description. It is the physician’s obligation to interpret this signal to elucidate the cause of the pain and then to alleviate it. If the cause of the pain is elusive, then it is the physician’s responsibility to relieve the pain to the best of his/her ability and within the limits of safety of the patient. On a routine basis, a physician causes pain as part of interventions (surgery and other procedures) to take care of some underlying process. In these situations, the cause of the pain is obvious, the pain is acute and it is the physician’s obligation to treat this pain to the best of his/her ability.
The management of pain has become increasingly important because patients have demanded that pain be controlled in a more effective manner. Pain is cultural, nonlinear, subjective and age- and gender-dependent, making its quantification difficult.(1–3) It is most commonly measured using some variation of a visual analogue scale.
Pain involves the nociception process, which begins with transduction, where the pain stimulus results in tissue damage and the onset of a nerve impulse. The nociception process continues with transmission.(2) Transmission occurs through the spinal cord up to the cerebral cortex. In the spinal cord, modulation of the pain message occurs, and when the pain message reaches the cerebral cortex, perception is achieved. Despite the fact that the key factor of importance in pain management is the area where the pain originates, the traditional target of pain management is primarily in the supratentorial region of the brain, through the use of narcotic (opioid) medication. While opioids act at other sites, including the site of damage, their primary site of action is the brain. A key factor in treating acute pain is to realise that the pain process can be affected at multiple levels between the site of transduction and the final reception in the cerebral cortex.
The multimodal approach
Acute pain can be treated more effectively by addressing it at multiple sites in the body – that is, peripherally at the site of tissue damage, during the transmission process, during the modulation process in the spinal cord or at the cerebral reception level.(4) Furthermore, pain medications differ in their mechanism of action, permitting the use of multiple drugs simultaneously to achieve better relief of pain with a lower side-effect profile.
Consequences of inadequately treated pain
Adequate treatment of pain will minimise the harmful physiological effects of acute pain. The type of surgical insult causing acute pain will produce varying harmful effects. Surgery in the abdominal cavity or thoracic area can produce pulmonary compromise, which can lead to atelectasis, hypoxia, hypocarbia, and even predispose the patient to infection. While surgery in other areas may not directly compromise pulmonary function, there will be increased sympathetic activity with unrelieved pain, which can lead to increased O(2) consumption, tachycardia and, because the coronary arteries fill during diastole, myocardial ischaemia. While young, robust patients have the pulmonary and cardiac reserve to tolerate tachycardia and increased O(2) consumption, older patients or those with coronary artery disease may suffer permanent disability from surgical interventions with inadequate pain relief.
Psychologically, patients with unrelieved pain have higher anxiety levels, which can lead to sleeplessness, more anxiety and a demoralised patient. A demoralised patient is a poor candidate for return to normal function in a timely manner. There are social consequences to inadequately treated acute pain. In the USA, public concern regarding unrelieved pain has resulted in litigation,(5) actions by medical boards against physicians(6) and legislation to address these issues. Legislation on the primary tools used in pain management, namely narcotics, has been conflicted. While the public, at least in the USA, is clamouring for better pain control and management,(7) implying easier access to narcotics, medical boards and law enforcement have made efforts to increase control over narcotics with the intent of preventing, or at least reducing, abuse of these euphoria-producing drugs.
Multimodal or “stacked” pain therapy
Acute postsurgical pain is best managed using a multimodal approach that “stacks” one means of achieving analgesia on another.(8) The summed effect of all modalities results, at lower dose levels, in better pain relief than any one modality could do at any dosage level because each one does its part by addressing the pain process at a different site in the nervous system. In contrast, traditional pain management after surgery has relied upon narcotics initially administered parenterally, and subsequently orally.
This traditional pharmacological approach now includes the use of narcotics and anaesthetics in the epidural space, the subarachnoid space and the wound. If pain relief was inadequate, higher doses of narcotic were administered, or given with medications that potentiate the effects, such as hydroxyzine. Increasing doses of narcotics can result in an increasing incidence of characteristic undesirable side-effects such as nausea, vomiting, constipation, disorientation and dysphoria (especially in older patients) and, perhaps of more concern, respiratory depression and hypoxia.(2) The use of multiple therapies at sub-maximal doses minimises the deleterious side-effects of any one of the modalities.(8,9) Stacked modalities include nonpharmacological techniques, such as cold therapy and immobilisation.
The transduction process is a key site for addressing the pain that has been relatively ignored in the past. Tissue damage causes an inflammatory process and a sensitising “soup” to be formed.(10) This “soup” is an acid environment with released histamine, cytokines, leukotrienes, neuropeptides, prostaglandins, norepinephrine, bradykinins and purines. Much of this sensitising “soup” can be addressed pre-emptively by the preoperative administration of prostaglandin inhibitors and/or gluco-corticoids such as dexamethasone.(11)
Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID) that has been available for many years for parenteral or oral use in post-operative analgesia. Many physicians have avoided its use because of its known effect of inhibiting platelet function, which can result in a significant increase in blood loss.(12) However, the advent of cyclo-oxygenase (cox)-2 inhibitors, which have essentially no effect on platelets at doses normally used, offered the opportunity to address the effects of inflammation and pain at the transduction site without the risk of increasing haemorrhage. Several research teams have reported on the use of cox-2 inhibitors to aid in postoperative analgesia. Reuben and Connelly, for example, demonstrated significant reductions in opiate use in patients undergoing spinal fusion surgery through the use of celecoxib and rofecoxib.(13)
Another means of addressing the transduction of the nociceptor is to instil a blocking agent, such as bupivicaine or clonidine,(8) through local injection or through a pump that continuously replenishes this drug at the site of action. The use of pain pumps is not limited to minimising the transduction process. When inserted near peripheral nerves, they can be used to block the transmission process.
Several studies have demonstrated the benefit of indwelling catheters adjacent to peripheral nerves.(3,14) The transmission–modulation process can be affected by the use of regional analgesia, such as continuous subarachnoid, or epidural anaesthetics, such as bupivicaine at low doses that do not impair motor function.
Alternatively, analgesics such as morphine placed at the time of the spinal anaesthetic in the sub-arachnoid space can provide postoperative analgesia for 12h or more. When narcotics are used in the spinal canal, pruritis, rash and gastrourinary (GU) retention are common problems. Modulation in the spinal canal area can also be affected by tramadol, which is a weak m-receptor but stimulates serotonin release and weak inhibition of norepinephrine and serotonin reuptake. Because this drug is now off-patent, it has a much better cost–benefit profile.
At the perception level, several drugs with different modes of action can be utilised. Acetaminophen is an excellent drug with an unknown mode of action (probably a central effect on brain prostaglandin synthase). It has no peripheral effect and is different from the action of nonsteroidals, opioids and tramadol. Thus, its action is additive to those of the other drugs. Furthermore, tramadol can also have a central effect on reducing pain. Finally, opioids can be highly effective in treating pain at the perception level, but at lower doses to minimise side-effects.
Several studies have shown the benefits of such an approach. For example, Skinner and Shintani used a pre-emptive, multimodal approach to control pain with the cox-2 inhibitor rofecoxib, in combination with narcotics, tramadol, dexamethasone, bupivicaine pain pumps and cold therapy, and demonstrated significant reductions in opiate use, improvements in pain scores, decreased hospital stay and increased patient satisfaction.(9) Aggressive, pre-emptive pain management can result in reduced pain sensitisation, less deleterious side-effects and increased patient satisfaction.
- Pain: The Fifth Vital Sign. American Pain Society. (W:www.ampainsoc.org/advocacy/fifth.htm).
- Ashburn MA, Rice L. The management of pain. Philadelphia: Churchill Livingstone; 1998.
- Allen H,et al. Anesth Analg 1998;87;93-7.
- Skinner HB. Am J Orthop 2004;33 Suppl: 5-9.
- Associated Press. $1.5 M awarded in pain therapy case: California jury rules man was undermedicated. 14 June 2003.
- Dahl JL. JAMA 2000;284:2785.
- Joranson DE, et al. JAMA 2000; 283:1710-4.
- Reuben SS, et al. J Bone Joint Surg Am 2000;82: 1754-66.
- Skinner HB, et al. Am J Orthop 2004;33:85-92.
- Mitchell VC, Raja SN. Preemptive analgesia – clinical studies. In: Benzon HT, Raja SN, Borsook D, Molloy RE, Strichartz G, editors. Essentials of pain medicine and regional anesthesia. Philadelphia: Churchill Livingstone;1999: 143-6.
- Carr MM, et al. Arch Otolaryngol Head Neck Surg 1999;125:1361-4.
- Fragen RJ, et al. J Bone Joint Surg Am 1995;77: 998-1002.
- Reuben SS, et al. Anesth Analg 2000;91:1221-5.
- Stevens RD, et al. Anesthesiology 2000;93:115-21.