|Year : 2015 | Volume
| Issue : 3 | Page : 105-110
Pain management following spinal surgeries: An appraisal of the available options
Sukhminder Jit Singh Bajwa1, Rudrashish Haldar2
1 Department of Anaesthesiology and Intensive Care, Gian Sagar Medical College and Hospital, Banur, Punjab, India
2 Department of Anaesthesiology, SGPGIMS, Lucknow, Uttar Pradesh, India
|Date of Web Publication||28-Jul-2015|
Dr. Sukhminder Jit Singh Bajwa
House No. 27-A, Ratan Nagar, Tripuri, Patiala - 147 001, Punjab
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Spinal procedures are generally associated with intense pain in the postoperative period, especially for the initial few days. Adequate pain management in this period has been seen to correlate well with improved functional outcome, early ambulation, early discharge, and preventing the development of chronic pain. A diverse array of pharmacological options exists for the effective amelioration of post spinal surgery pain. Each of these drugs possesses inherent advantages and disadvantages which restricts their universal applicability. Therefore, combination therapy or multimodal analgesia for proper control of pain appears as the best approach in this regard. The current manuscript discussed the pathophysiology of postsurgical pain including its nature, the various tools for assessment, and the various pharmacological agents (both conventional and upcoming) available at our disposal to respond to post spinal surgery pain.
Keywords: Hyperalgesia, infusion, intravenous, multimodal analgesia, pain management, pain measurement, spinal surgery
|How to cite this article:|
Bajwa SS, Haldar R. Pain management following spinal surgeries: An appraisal of the available options. J Craniovert Jun Spine 2015;6:105-10
|How to cite this URL:|
Bajwa SS, Haldar R. Pain management following spinal surgeries: An appraisal of the available options. J Craniovert Jun Spine [serial online] 2015 [cited 2021 Oct 20];6:105-10. Available from: https://www.jcvjs.com/text.asp?2015/6/3/105/161589
| Introduction|| |
Baring few exceptions, spinal surgeries are mostly elective in nature.  Commonly performed spinal surgeries include laminectomies, discectomies, spinal fusions, instrumentations, scoliosis corrections, and spinal tumor excision. Conventional spinal surgeries (nonminimally invasive) often involve extensive dissection of subcutaneous tissues, bones, and ligaments and thus result in a considerable degree of postoperative pain. The pain is severe and typically lasts for 3 days.  Adequate pain relief is, therefore, an important facet of postoperative care of these patients. Adequate pain treatment in these patients is compounded by the fact that the majority of these patients had already suffered from preexisting chronic pain that had been treated with conventional analgesics or narcotics. The preexisting pain along with long-term consumption of analgesics and/or opioids alters pain perception in these patients thereby complicating pain management. , Effective pain controls facilitates early mobilization as well as expedites hospital discharge. This review attempts to discuss the physiological basis of pain following spinal surgeries, assessment of postoperative pain and also analyze the different aspects of the conventional therapies employed for relief from postoperative pain following spinal surgeries.
| Physiological Genesis and Characteristics of Pain following Spinal Surgeries|| |
Postoperative pain is the result of activation of various pain mechanisms including nociceptive, neuropathic, and inflammatory.  Pain from the back originates from different tissues such as vertebrae, intervertebral discs, ligaments, dura, nerve root sleeves, facet joint capsules, fascia, and muscles. Various nociceptors and mechanoreceptors that are capable of eliciting pain transmit these sensations. Innervation of these structures is via the posterior rami of spinal nerves connected to sympathetic and parasympathetic nerves. Mechanical irritation, compression or postoperative inflammation causes pain. Since extensive cross connectivity of these nerves exists, referred pain is a common occurrence. As compared to postoperative pain, patients with preexisting chronic pain mostly complain of referred pain rather than local or diffuse pain. However, in the postoperative period, pain is more localized and in subjects where referred pain persisted, their visual analog scale (VAS) scores tend to be elevated.  The intensity of postoperative pain is directly proportional to the number of vertebrae involved in the surgery.  Peripheral as well as central sensitization further contributes to the development of increased pain. Moreover, the region of surgery does not seem to have a bearing on the pain severity, and it is similar in surgeries of cervical, thoracic or lumbar spine. , Postoperative pain differs from chronic pain in that it is transitory, and gradual improvement occurs in due course of time. This characteristic makes it further amenable to medical therapy as compared to the chronic pain. 
| Measurement of Pain following Spinal Surgeries|| |
Accurate measurement of postoperative pain is imperative to provide optimum pain relief. Instruments to evaluate pain should be able to measure intensity, quality, its effect on function and quality of life, and the objective assessment of the amount of pain medications. A variety of pain assessment tools can be utilized to quantify the pain in its different dimensions so that appropriate remedial measures can be undertaken. The numerical rating scale and the VAS are well-validated tools to quantify the intensity of pain. More comprehensive and multidimensional inventories like McGill pain questionnaire helps in estimating the neurophysiological and psychological domains of pain.  It allows to identify the location and quality of pain. The Brief Pain Inventory aids in evaluating the effect of pain on general activity, mood, ambulation, relationships, sleep, and work enjoyment. The Roland Morris disability questionnaire and Oswestry disability index (ODI)/neck disability index (NDI) are validated systems that can be utilized in patients with back pain to ascertain their levels of disability due to pain. ODI is favored over Rolland-Morris score because of its feasibility and responsiveness in disabled patients.  NDI is a modification of ODI utilized in patients with cervical ailments.  For objective assessment of pain medication usage, all narcotic medications can be converted into their respective morphine sulfate equivalents using an equianalgesic dose table where pain relief with 10 mg parenterally administered morphine is used as a reference standard. 
| Pain Management Strategies following Spinal Surgeries|| |
Parenteral and oral modalities
Narcotic analgesics are common and efficacious drugs for the treatment of severe pain and provide excellent pain relief. However, their widespread employment is limited by their unpleasant side effects like respiratory depression, nausea, vomiting, and other opioid-related adverse events. Intramuscular or intravenous delivery of narcotic analgesics provides reasonable degree of analgesia, however, patient-controlled analgesia (PCA) has established superiority in terms of quality of analgesia and ease of use as compared to intermittent divided dosing. Among narcotics, morphine is the first line therapy in the absence of any contraindications or previous adverse effects. Oxycodone affords better control of hallucinations; however, other side effects are similar. Methadone, which is often used as a replacement opioid in therapy for opioid dependency, has been investigated for pain relief following thoracolumbar surgeries. A single perioperative dose reduced the pain scores and narcotic requirement for 72 h following multilevel spinal surgeries.  Being a noncompetitive N-Methyl-D-aspartate (NMDA) receptor antagonist, , it mitigates pain and also reduces (or prevents) opioid tolerance.  Its long duration of action decreases the need of PCA. Dosing modifications are needed for patients who have developed tolerance because of their preexisting chronic pain. Their baseline narcotic requirements should be replaced or maintained. The opioid administration should be aimed to be stopped by a particular due date, and opioid requirements should be reassessed during discharge. Patients may require oral narcotic medications following discharge therefore laxatives and antiemetics should be concurrently prescribed.
Nonsteroidal antiinflammatory drugs
These drugs act by blocking cyclooxygenase (COX) enzyme and the subsequent prostaglandin production and inflammatory pathways. They have proven efficacy in ameliorating postoperative pain,  and especially pain following spinal surgeries. ,, Nonsteroidal antiinflammatory drugs (NSAID's) reduce pain, inflammation, fever, and improve postoperative ambulation following spinal surgeries. Exclusive use of NSAID's for providing postoperative analgesia is, however, questionable. Nevertheless, ample support exists that their concomitant administration along with opioids provides better analgesia as compared to either of the two classes of drugs alone. ,, NSAID's can be administered either intravenously (ketorolac, ketoprofen, diclofenac) or orally (ibuprofen, diclofenac, mefenamic acid). Ketorolac provides acceptable degree of analgesia and also has opioid sparing effects. ,, NSAID's are also effective in providing analgesia for pediatric patients undergoing spinal surgeries as adjuvants to opioids providing lower pain scores and fewer opioids related side effects. ,, NSAID's are generally started within 3 days after surgery and continued for 3 or more days. Platelet dysfunction, risk of hemorrhage, gastric ulceration, and renal toxicity are known side effects of these drugs.  Importantly, concerns have been raised regarding the effects of NSAID's on bone metabolism and osteoblastic proliferation.  However, increasing evidence has been gathered over the past few years that impaired bone healing is dependent upon higher doses (120-240 mg/day)  and longer duration  of treatment with ketorolac. COX-2 inhibitors (parecoxib, celecoxib) are a subclass of NSAID's which by their selective action preserves platelet function and gastric mucosa. They are preferred where hemostasis is a cause of concern. However, COX-2 dependent production of PGE2 is essential for adequate skeletal regeneration. This decremental effect in osteogenetic potential limits their widespread applicability. Though it had been demonstrated that celecoxib administration 1 h before induction and 12 h thereafter for next 5 days improved pain scores and reduced opioid consumption following spinal fusion surgery without effecting the rates of nonunion.  COX-2 inhibitors are contraindicated in renal dysfunction are should be used cautiously in patients with history of coronary and cerebrovascular diseases.  Additionally, all NSAID's can increase the risk of sodium and water absorption increasing the risk of exacerbating hypertension and heart failure.
Paracetamol and its prodrug acetaminophen have gained prominence as an efficacious, safe, and cheaper modality to treat postoperative pain when used intravenously. It is helpful in providing analgesia in the immediate postoperative period when gastrointestinal motility is reduced or when rapid analgesia establishment is required. The onset of analgesia begins within 5-10 min of intravenous paracetamol administration. Mechanisms of action of paracetamol are speculative and may involve central and peripheral sites of action, , inhibition of prostaglandins,  and inhibition of descending serotoninergic pathways.  Paracetamol as the sole agent may not be useful as an analgesic agent , nonetheless combination therapy with opioids have shown to result in decreasing opioid consumption substantially. , In spite of the popular perception that acetaminophen has opioid sparing effects, some authors have contradicted the claims of reduction in opioid consumption following administration of acetaminophen. Hiller et al. demonstrated that even though the use of acetaminophen as an adjuvant provided enhanced pain relief, the consumption of oxycodone did not decrease.  Paracetamol offers a safer option for analgesia in patients where NSAID's need to be avoided in view of bleeding risks, asthma, or renal derangements.
Ketamine is helpful for attenuation of postoperative pain by its direct analgesic effects and preventing the nociceptive pathway sensitization in the central nervous system. Being a NMDA receptor antagonist, it is believed to reduce or reverse opioid tolerance in patients who are chronic opioid users. The suggested contribution of NMDA receptors in opioid tolerance and development of hyperalgesia supports the effectiveness of subanesthetic doses of ketamine in alleviating postsurgical pain. Studies on patients undergoing spinal surgeries have not yielded any definitive results.  Loftus et al. had demonstrated the reduction in postoperative narcotic demand following intraoperative ketamine administration without any side effects.  Subramaniam et al. however contradict this view through their investigation that failed to demonstrate any improvement in analgesia following intraoperative and postoperative infusions.  Dysphoria, sedation, diplopia, salivation, nausea, and hallucination restrict the extensive utilization of this drug in pain management practice.
Steroid therapy has been postulated to reduce inflammation and reduce scar tissue formation that contributes to postoperative pain. Apart from the anti-inflammatory effects steroids also inhibit expression of phospholipase A2 and supposedly decrease the release of substance P at the dorsal root ganglion.  Investigations conducted by Aminmansour et al. had revealed that intravenous administration of 40 mg dexamethasone intraoperatively reduces radicular pain and opioid requirement following surgery for herniated disc.  Similar findings were reported by Watters et al. where oral and intravenous steroid administration reduced pain scores, narcotic consumption, and hospital stay.  Intraoperative irrigation with dexamethasone also reduced the duration of hospitalization and narcotic consumption following microdiscectomy. 
Intrathecal drug administration
Local anesthetics are the commonly used drugs administered via intrathecal route. Other drugs used through this route include opioids and steroids.  Local anesthetics as the sole agent has the drawback of causing motor and sensory block that hinders adequate neurological assessment. Intrathecal morphine and fentanyl can reduce the cumulative opioid demand in patients after spinal surgery. , However, intrathecal opioids, especially morphine can cause late respiratory depression owing to its hydrophilicity and cephalad diffusion through cerebrospinal fluid. Thus, vigilant monitoring is necessary. Combining local anesthetics with opioids provides synergistic effects that reduced opioid dosage and side effects.
Epidural drug administration
Epidural drug administration provides good safety, extended analgesia and decreased incidences of respiratory and thromboembolic events making it a promising route of drug delivery for postoperative analgesia. Epidural analgesia produces substantial reduction in pain scores and narcotic consumption. Local anesthetics, narcotics, and steroids are the usual drugs that are used epidurally. Epidural administration of drugs is through different techniques such as single and double catheters, intermittent boluses, PCA devices, or continuous infusions. Epidural catheters can be placed intraoperatively by surgeons under direct vision which increases the success rates. Local anesthetics used exclusively carries the risk of motor block and sympathectomy mediated hypotension. Compared to bupivacaine, ropivacaine offers better systemic safety margin and higher selectivity toward sensory fibers. Opioids can also be administered solely or in combination with local anesthetic solutions. Opioids modify the nociceptive input at the levels of dorsal horn receptors. Guilfoyle et al. found lower VAS scores following epidural use of fentanyl boluses in patients undergoing lumbar decompression.  Use of opioid only solution through epidural route can predispose to side effects such as nausea, vomiting, and pruritus. Combination solution of opioids and local anesthetics avoids these effects, lowers dosage of parenteral opioids,  and provides better quality of analgesia. , Moreover, the relief from dynamic pain is enhanced following use of combination solutions. O'Hara et al. and Fisher et al. , showed that both intravenous PCA and epidural PCA are equally effective; however, greater incidences of side effects were seen in the epidural group.  As with intrathecal usage, epidural administration of opioids should be monitored cautiously to prevent inadvertent respiratory depression due to the diffusion of opioids in cerebrospinal fluid. Epidural administration of steroids is also a promising option as steroids reduce immediate and late pain due to peridural fibrosis. They significantly decrease the analgesic consumption and length of hospital stay following lumbar spinal surgeries.  Adverse events like postoperative wound infection have been rare complications with their usage. Cautious use of epidural techniques is advocated in patients on chronic anticoagulant therapy and those receiving anti platelet drugs considering the risk of developing spinal hematoma.
Newer possibilities for postspinal surgery pain management
Alpha 2 adrenoreceptor antagonists
Both clonidine and dexmedetomidine have emerged as effective agents for providing analgesia post spinal surgery. Use of these agents as adjuncts to local anesthetics, opioids or their combination enhances the analgesic properties. Hemodynamic stability and lack of respiratory depression are added advantages of these drugs. Clonidine has been utilized for providing postoperative analgesia through various methods. Administered epidurally, along with subcutaneous bupivacaine at the incision site has shown better analgesia and hemodynamic stability in spinal surgery patients.  Double catheter approaches using bupivacaine, fentanyl, and clonodine has shown encouraging results.  It has also been seen to reduce morphine requirements by 43% in the first 36 h following spinal surgeries. 
The higher affinity and selectivity of dexmedetomidine aid in decreasing the dosages as well as adverse effects of local anesthetics and opioids when used simultaneously with dexmedetomidine. As an adjunct to propofol based total intravenous anesthesia, it has been found to reduce postoperative pain beyond the immediate postoperative period (48 h) and reducing PCA requirements. Dexmedetomidine presumably acts on the nociceptive cascade and prevents the sensitization of nociceptors present in the dorsal horn. Moreover, the opioid-induced hyperalgesia that might occur following intraoperative opioid usage can be negated using a dexmedetomidine based infusion intraoperatively which extends its effect beyond its duration of action.  When used concurrently with inhalation anesthetics in the form of intravenous infusion, dexmedetomidine reduced analgesic needs postoperatively.  Early recovery provided with dexmedetomidine also allowed early neurological assessment that is important following spinal surgeries.
Transcutaneous electrical nerve stimulation
It has been investigated to be an efficient and opioid sparing method for providing analgesia following major spinal surgery. Transcutaneous electrical nerve stimulation (TENS) applied preincisionally and postoperatively reduces the postoperative opioid requirement and provides sufficient analgesia. However, the beneficial effects of TENS on cognitive functions could not be demonstrated. 
Extended release formulations
These drugs have generated interest because of their longer duration of action. Multivesicular liposomes containing bupivacaine produces sustained release of drugs in the vicinity of the surgical site.  Single dose administration at the surgical site produces analgesia for several days. The effectiveness of these liposomes has been seen in various surgeries; however, their application in spinal surgeries has not been studied. Similar to them, extended release epidural morphine has been developed which can be administered at the lumbar level. Longer lasting analgesia (up to 48 h),  lower systemic concentrations of morphine and better patient activity levels  are the advantages offered by this modality which makes it a novel and emerging approach to manage post spinal surgery pain.
| The Challenge for the Future Research|| |
A recent review of 179 surgical procedures has rated spinal surgeries among the top six procedures causing highest degree of postsurgical pain.  Adequate and energetic pain management is imperative to improve the functional outcome after surgery. As inadequately treated postsurgical pain contributes to longer hospital stays, slower progress in ambulation, respiratory complications, venous thrombosis, development of chronicity functional deficits and finally elevated cost of treatment, the importance of managing postsurgical pain following spinal surgery cannot be underestimated. Despite improvements in pain management therapies and drugs, a single drug or therapy is yet to be labeled as the "gold standard" for pain control following spinal surgery and wide-ranging differences exist in treatment modalities among different centers. Experts strongly suggest the inclusion of multimodal analgesia for the management of such patients as the quality of analgesia is improved vastly and the side effects of individual drugs diminish. Moreover, the dependence on opioid also reduces markedly. Thus, it appears as the ideal strategy in the present times. Although multimodal analgesia is the recommended strategy for postoperative analgesia, lack of consensus also exists on the appropriate multimodal analgesia protocols or algorithms.  The identification and utilization of such strategies should be the direction of future research.
| Conclusion|| |
Effective pain control aided by the judicious use of different pain control therapies can significantly improve the overall success of the surgery. Keeping a proper pain control plan following surgery and discussing it with the patient so that realistic expectations are set in place about the type and level of pain can go a long way in improving the comfort and satisfaction of the patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Chou R, Baisden J, Carragee EJ, Resnick DK, Shaffer WO, Loeser JD. Surgery for low back pain: A review of the evidence for an American Pain Society Clinical Practice Guideline. Spine (Phila Pa 1976) 2009;34:1094-109.
Bianconi M, Ferraro L, Ricci R, Zanoli G, Antonelli T, Giulia B, et al.
The pharmacokinetics and efficacy of ropivacaine continuous wound instillation after spine fusion surgery. Anesth Analg 2004;98:166-72.
Bhaskar SB, Bajwa SS. Pharmaco genomics and anaesthesia: Mysteries, correlations and facts. Indian J Anaesth 2013;57:336-7.
Loftus RW, Yeager MP, Clark JA, Brown JR, Abdu WA, Sengupta DK, et al.
Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology 2010;113:639-46.
Mathiesen O, Dahl B, Thomsen BA, Kitter B, Sonne N, Dahl JB, et al.
A comprehensive multimodal pain treatment reduces opioid consumption after multilevel spine surgery. Eur Spine J 2013;22:2089-96.
Klimek M, Ubben JF, Ammann J, Borner U, Klein J, Verbrugge SJ. Pain in neurosurgically treated patients: A prospective observational study. J Neurosurg 2006;104:350-9.
Bernard JM, Surbled M, Lagarde D, Trennec A. Analgesia after surgery of the spine in adults and adolescents. Cah Anesthesiol 1995;43:557-64.
Bajwa SJ, Kulshrestha A. Spine Surgeries: Challenging Aspects and Implications for Anaesthesia. J Spine Neurosurg 2013;2:3. doi:10.4172/2325-9701.1000114.
Jaffe RA, Samuels SI. Anesthesiologist′s Manual of Surgical Procedures. 3 rd
ed. Philadelphia: Lippincott Williams & Wilkins; 2004.
Nasir M, Latif K, Ahmad MJ. Pre-emptive pain control: Comparison of ketorolac and diclofenac sodium. Prof Med J 2007;14:591-7.
Melzack R. The mcgill pain questionnaire: Major properties and scoring methods. Pain 1975;1:277-99.
DeVine J, Norvell DC, Ecker E, Fourney DR, Vaccaro A, Wang J, et al.
Evaluating the correlation and responsiveness of patient-reported pain with function and quality-of-life outcomes after spine surgery. Spine (Phila Pa 1976) 2011;36:S69-74.
Vernon H, Mior S. The neck disability index: A study of reliability and validity. J Manipulative Physiol Ther 1991;14:409-15.
Berdine HJ, Nesbit SA. Equianalgesic dosing of opioids. J Pain Palliat Care Pharmacother 2006;20:79-84.
Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg 2011;112:218-23.
Fishman SM, Wilsey B, Mahajan G, Molina P. Methadone reincarnated: novel clinical applications with related concerns. Pain Med 2002;3:339-48.
Davis MP, Walsh D. Methadone for relief of cancer pain: A review of pharmacokinetics, pharmacodynamics, drug interactions and protocols of administration. Support Care Cancer 2001;9:73-83.
Inturrisi CE. Clinical pharmacology of opioids for pain. Clin J Pain 2002;18:S3-13.
Dumont AS, Verma S, Dumont RJ, Hurlbert RJ. Nonsteroidal anti-inflammatory drugs and bone metabolism in spinal fusion surgery: A pharmacological quandary. J Pharmacol Toxicol Methods 2000;43:31-9.
Nissen I, Jensen KA, Ohrström JK. Indomethacin in the management of postoperative pain. Br J Anaesth 1992;69:304-6.
Reuben SS, Connelly NR, Steinberg R. Ketorolac as an adjunct to patient-controlled morphine in postoperative spine surgery patients. Reg Anesth 1997;22:343-6.
Turner DM, Warson JS, Wirt TC, Scalley RD, Cochran RS, Miller KJ. The use of ketorolac in lumbar spine surgery: A cost-benefit analysis. J Spinal Disord 1995;8:206-12.
Jirarattanaphochai K, Jung S. Nonsteroidal antiinflammatory drugs for postoperative pain management after lumbar spine surgery: A meta-analysis of randomized controlled trials. J Neurosurg Spine 2008;9:22-31.
Le Roux PD, Samudrala S. Postoperative pain after lumbar disc surgery: A comparison between parenteral ketorolac and narcotics. Acta Neurochir (Wien) 1999;141:261-7.
Sevarino FB, Sinatra RS, Paige D, Ning T, Brull SJ, Silverman DG. The efficacy of intramuscular ketorolac in combination with intravenous PCA morphine for postoperative pain relief. J Clin Anesth 1992;4:285-8.
Gwirtz KH, Kim HC, Nagy DJ, Young JV, Byers RS, Kovach DA, et al.
Intravenous ketorolac and subarachnoid opioid analgesia in the management of acute postoperative pain. Reg Anesth 1995;20:395-401.
Eberson CP, Pacicca DM, Ehrlich MG. The role of ketorolac in decreasing length of stay and narcotic complications in the postoperative pediatric orthopaedic patient. J Pediatr Orthop 1999;19:688-92.
Munro HM, Walton SR, Malviya S, Merkel S, Voepel-Lewis T, Loder RT, et al.
Low-dose ketorolac improves analgesia and reduces morphine requirements following posterior spinal fusion in adolescents. Can J Anaesth 2002;49:461-6.
Sutters KA, Shaw BA, Gerardi JA, Hebert D. Comparison of morphine patient-controlled analgesia with and without ketorolac for postoperative analgesia in pediatric orthopedic surgery. Am J Orthop (Belle Mead NJ) 1999;28:351-8.
Sinatra RS, Torres J, Bustos AM. Pain management after major orthopaedic surgery: Current strategies and new concepts. J Am Acad Orthop Surg 2002;10:117-29.
Reuben SS, Ablett D, Kaye R. High dose nonsteroidal anti-inflammatory drugs compromise spinal fusion. Can J Anaesth 2005;52:506-12.
Li Q, Zhang Z, Cai Z. High-dose ketorolac affects adult spinal fusion: A meta-analysis of the effect of perioperative nonsteroidal anti-inflammatory drugs on spinal fusion. Spine (Phila Pa 1976) 2011;36:E461-8.
Reuben SS, Ekman EF. The effect of cyclooxygenase-2 inhibition on analgesia and spinal fusion. J Bone Joint Surg Am 2005;87:536-42.
Moore UJ, Marsh VR, Ashton CH, Seymour RA. Effects of peripherally and centrally acting analgesics on somato-sensory evoked potentials. Br J Clin Pharmacol 1995;40:111-7.
Piletta P, Porchet HC, Dayer P. Central analgesic effect of acetaminophen but not of aspirin. Clin Pharmacol Ther 1991;49:350-4.
Flower RJ, Vane JR. Inhibition of prostaglandin synthetase in brain explains the anti-pyretic activity of paracetamol (4-acetamidophenol). Nature 1972;240:410-1.
Tjølsen A, Lund A, Hole K. Antinociceptive effect of paracetamol in rats is partly dependent on spinal serotonergic systems. Eur J Pharmacol 1991;193:193-201.
Hans P, Brichant JF, Bonhomme V, Triffaux M. Analgesic efficiency of propacetamol hydrochlorid after lumbar disc surgery. Acta Anaesthesiol Belg 1993;44:129-33.
Yilmaz MZ, Sarihasan BB, Kelsaka E, Tas N, Torun AC, Koksal E, et al
. Comparison of the analgesic effects of paracetamol and tramadol in lumbar disc surgery. Turk J Med Sci 2015;45:438-42.
Dahl V, Raeder JC. Non-opioid postoperative analgesia. Acta Anaesthesiol Scand 2000;44:1191-203.
Toygar P, Akkaya T, Ozkan D, Ozel O, Uslu E, Gümüs H. Does iv paracetamol have preemptive analgesic effect on lumber disc surgeries? Agri 2008;20: 14-9.
Hiller A, Helenius I, Nurmi E, Neuvonen PJ, Kaukonen M, Hartikainen T, et al.
Acetaminophen improves analgesia but does not reduce opioid requirement after major spine surgery in children and adolescents. Spine (Phila Pa 1976) 2012;37:E1225-31.
Grathwohl KW. Does ketamine improve postoperative analgesia? More questions than answers. Pain Med 2011;12:1135-6.
Subramaniam K, Akhouri V, Glazer PA, Rachlin J, Kunze L, Cronin M, et al.
Intra- and postoperative very low dose intravenous ketamine infusion does not increase pain relief after major spine surgery in patients with preoperative narcotic analgesic intake. Pain Med 2011;12:1276-83.
Wong HK, Tan KJ. Effects of corticosteroids on nerve root recovery after spinal nerve root compression. Clin Orthop Relat Res 2002;403:248-52.
Aminmansour B, Khalili HA, Ahmadi J, Nourian M. Effect of high-dose intravenous dexamethasone on postlumbar discectomy pain. Spine (Phila Pa 1976) 2006;31:2415-7.
Watters WC 3 rd
, Temple AP, Granberry M. The use of dexamethasone in primary lumbar disc surgery. A prospective, randomized, double-blind study. Spine (Phila Pa 1976) 1989;14:440-2.
Foulkes GD, Robinson JS Jr. Intraoperative dexamethasone irrigation in lumbar microdiskectomy. Clin Orthop Relat Res 1990;261:224-8.
Langmayr JJ, Obwegeser AA, Schwarz AB, Laimer I, Ulmer H, Ortler M. Intrathecal steroids to reduce pain after lumbar disc surgery: A double-blind, placebo-controlled prospective study. Pain 1995;62:357-61.
Ziegeler S, Fritsch E, Bauer C, Mencke T, Müller BI, Soltesz S, et al.
Therapeutic effect of intrathecal morphine after posterior lumbar interbody fusion surgery: A prospective, double-blind, randomized study. Spine (Phila Pa 1976) 2008;33:2379-86.
Chan JH, Heilpern GN, Packham I, Trehan RK, Marsh GD, Knibb AA. A prospective randomized double-blind trial of the use of intrathecal fentanyl in patients undergoing lumbar spinal surgery. Spine (Phila Pa 1976) 2006;31:2529-33.
Guilfoyle MR, Mannion RJ, Mitchell P, Thomson S. Epidural fentanyl for postoperative analgesia after lumbar canal decompression: A randomized controlled trial. Spine J 2012;12:646-51.
Bajwa SJ. Rare and Serious Side Effects in Chronic Pain after Opioids. J Pain Relief, 2012;1:106.
Schenk MR, Putzier M, Kügler B, Tohtz S, Voigt K, Schink T, et al.
Postoperative analgesia after major spine surgery: Patient-controlled epidural analgesia versus patient-controlled intravenous analgesia. Anesth Analg 2006;103:1311-7.
Lowry KJ, Tobias J, Kittle D, Burd T, Gaines RW. Postoperative pain control using epidural catheters after anterior spinal fusion for adolescent scoliosis. Spine (Phila Pa 1976) 2001;26:1290-3.
O′Hara JF Jr, Cywinski JB, Tetzlaff JE, Xu M, Gurd AR, Andrish JT. The effect of epidural vs intravenous analgesia for posterior spinal fusion surgery. Paediatr Anaesth 2004;14:1009-15.
Fisher CG, Belanger L, Gofton EG, Umedaly HS, Noonan VK, Abramson C, et al.
Prospective randomized clinical trial comparing patient-controlled intravenous analgesia with patient-controlled epidural analgesia after lumbar spinal fusion. Spine (Phila Pa 1976) 2003;28:739-43.
Ranguis SC, Li D, Webster AC. Perioperative epidural steroids for lumbar spine surgery in degenerative spinal disease. A review. J Neurosurg Spine 2010;13:745-57.
Jellish WS, Abodeely A, Fluder EM, Shea J. The effect of spinal bupivacaine in combination with either epidural clonidine and/or 0.5% bupivacaine administered at the incision site on postoperative outcome in patients undergoing lumbar laminectomy. Anesth Analg 2003;96:874-80.
Ekatodramis G, Min K, Cathrein P, Borgeat A. Use of a double epidural catheter provides effective postoperative analgesia after spine deformity surgery. Reg Anesth Pain Med 2002;49:173-7.
Farmery AD, Wilson-MacDonald J. The analgesic effect of epidural clonidine after spinal surgery: A randomized placebo-controlled trial. Anesth Analg 2009;108:631-4.
Hwang W, Lee J, Park J, Joo J. Dexmedetomidine versus remifentanil in postoperative pain control after spinal surgery: A randomized controlled study. BMC Anesthesiol 2015;15:21.
Keles GT, Ozer M, Dede G, Temiz C, Horasan GD, Civi M, et al
. Balanced anesthesia with dexmedetomidine added desflurane or sevoflurane in spinal surgery. J Anesth Clin Res 2012;3:216.
Unterrainer AF, Uebleis FX, Gross FA, Werner GG, Krombholz MA, Hitzl W. TENS compared to opioids in postoperative analgesic therapy after major spinal surgery with regard to cognitive function. Middle East J Anaesthesiol 2012;21:815-21.
Tong YC, Kaye AD, Urman RD. Liposomal bupivacaine and clinical outcomes. Best Pract Res Clin Anaesthesiol 2014;28:15-27.
Hartrick CT, Hartrick KA. Extended-release epidural morphine (DepoDur): Review and safety analysis. Expert Rev Neurother 2008;8:1641-8.
Carvalho B, Riley E, Cohen SE, Gambling D, Palmer C, Huffnagle HJ, et al.
Single-dose, sustained-release epidural morphine in the management of postoperative pain after elective cesarean delivery: Results of a multicenter randomized controlled study. Anesth Analg 2005;100:1150-8.
Gerbershagen HJ, Aduckathil S, van Wijck AJ, Peelen LM, Kalkman CJ, Meissner W. Pain intensity on the first day after surgery: A prospective cohort study comparing 179 surgical procedures. Anesthesiology 2013;118:934-44.
Devin CJ, McGirt MJ. Best evidence in multimodal pain management in spine surgery and means of assessing postoperative pain and functional outcomes. J Clin Neurosci 2015;22:930-38.