There is no type of pain ever investigated with scientific studies in which opiates have ever been found to be better than readily available non-narcotic alternatives.  There has never been a single study in which patients who had reportedly failed on non-narcotic pain medication were then randomly assigned to a different non-narcotic vs. a narcotic pain relievers.  Available research strongly suggests that the non-narcotic pain strategy would be more effective and, of course, with no risk of addiction.

Arthritis: Intra-Articular Morphine No Better Than Dexamethasone: In a DB PC study of 44 patients with chronic arthritis, intraarticular morphine (3 mg) did no better at pain relief during the first 6 hours or first 5 days than dexamethasone (4 mg)  although both did better than placebo. and saline (3 ml) in 44 patients with chronic inflammatory arthritis or osteoarthritis of the knee. Intraarticular morphine versus dexamethasone in chronic arthritis. Stein A, et al. Universitat Munchen, Klinische Immunologie, Germany. Pain. 1999 Dec;83(3):525-32.

Arthritis: Caffeine as Good as Propoxyphene When Added to Acetaminophen: In a 7-day DB French study of 124 adults, mostly with lower back pain, 51% of those with the caffeine vs. 47% of those with the dextropropoxyphene had a major reduction (>50%) in pain. Kuntz D, et al. Paris. Analgesic effect and clinical tolerability of the combination of paracetamol 500 mg and caffeine 50 mg vs. paracetamol and dextropropoxyphene. Presse Med 1996;25(25):1171-4. 

Arthritis: Diclofenac Better than Dextropropoxyphene with Acetaminophen: In a DB study of 846 pains with hip, knee, ankle, and/or wrist pain, diclofenac-SR 100 mg daily reduced pain 8% better than dextropropoxyphene 180 mg with acetaminophen 1950 mg/day (p<0.05). Diclofenac resulted in less time lost from work (p<0.05). Dextropropoxphene patients suffered more tiredness, sleep disturbance (50 vs. 21, p<0.01) while diclofenac had more abdominal or epigastric pain or indigestion (40 vs. 18, p<0.01). Parr G, et al. Br J Clin Pharmacol 1989;27(2):235-42.

Arthritis: Suprofen as Effective as Propoxyphene with Non-Significantly More Propoxyphene Dropouts: In a DB study of 114 patients with osteoarthritis, suprofen 200 mg q.i.d. did as well as propoxyphene 65 mg q.i.d. at relieving pain. Of suprofen patients, 24% discontinued therapy vs. 34% of propoxyphene primarily due to GI complaints. Salzman RT, et al. Pharmacology 1983;27 Suppl 1:55-64.

Biliary Colic: Ketorolac as Good as Meperidine with Fewer Side-Effects: In a DB study of 324 adults with biliary colic, IV ketorolac 30 mg did just as well as IV meperidine 50 mg. The change in the pain scores at time 2 h was 6.2 cm for the ketorolac group, compared with 6.7 cm cm for the meperidine group, not a significant difference (p = 0.25). Patients receiving meperidine reported markedly higher incidences of nausea and  dizziness (p = 0.009 and 0.003). Researchers conclude the results favor ketorolac. Comparison of intravenous ketorolac and meperidine in the treatment of biliary colic. Henderson SO, et al. University of Southern California. J Emerg Med 2002 Oct;23(3):237-41.

Biliary Colic: No Difference Between Ketorolac and Meperidine for Pain: In a DB study of 30 patients in the emergency room with acute biliary colic, meperidine 1.5 mg/kg up to 100 mg or ketorolac 60 mg IM, pain relief at time 30 min was 3.8 in the ketorolac group and 3.9 in the meperidine group. Rescue medication for additional analgesia at 30 min was used in 4 patients in the meperidine group and in 2 patients in the ketorolac group (28.6% vs. 12.5%, respectively; NS). A prospective study comparing i.m. ketorolac with i.m. meperidine in the treatment of acute biliary colic. Dula DJ, et al. Geisinger Medical Center, Danville, PA. J Emerg Med 2001 Feb;20(2):121-4.

Biliary Colic: Pentazocine Inferior to NSAID Flurbiprofen: In a DB study of 84 adults with intense biliary colic pain, the NSAID flurbiprofen 150 mg IM resulted in less pain within 30 minutes than 20 mg of N-hyoscine butylbromide or 30 mg of pentazocine. The superior benefit continued for the entire 6 hours of the study. Pentazocine had significantly more side-effect than the other 2 treatments (p < 0.02). The efficacy of injectable flurbiprofen in the symptomatic treatment of biliary colic. Camp Herrero J, et al. Hospital Clinic i Provincial, Barcelona. Med Clin (Barc) 1992 Feb 15;98(6):212-4.

Burns: Animal Study Finds Opiates Cause Post-Burn Immune Dysfunction: Alexander M, et al. Univ Alabama, Birmingham. J Surg Res 2005;129:161-8.

Colonoscopy: Meperidine No Added Value for Patients Given Midazolam: In a DB PC study of 100 adults undergoing colonoscopies, midazolam plus placebo was compared to midazolam plus meperidine. There were no significant difference of grade of tolerance, pain and willingness to another colonoscopy between the two groups. After the colonoscopy, systolic blood pressure, oxygen saturation, and pulse rate were significantly decreased (p<0.05) in both groups with no differences. Adding meperidine to the midazolam before the colonoscopy does not seem to bring more beneficial effect to patients. Comparison of midazolam versus midazolam/meperidine during colonoscopy in a prospective, randomized, double-blind study. Jung HK, et al. Ewha Womans University, Seoul, Korea. . Korean J Gastroenterol 2004 Feb;43(2):96-103.

Colonoscopy Pain: Meperidine Added Benefit: In a DB study of 253 patients undergoing colonoscopy, a single rapid intravenous bolus of 5 mg of midazolam did not do as well as 5 mg midazolam plus 50 mg meperidine. More patients (19%) in without meperidine reported moderate or severe pain (28% vs. 9%; p < 0.001), poor or unbearable tolerance (18% vs. 6%; p < 0.01) and unwillingness to undergo colonoscopy again in the future (14% vs. 5%; p < 0.05). Single bolus of midazolam versus bolus midazolam plus meperidine for colonoscopy: a prospective, randomized, double-blind trial. Radaelli F, et al. Valduce Hospital, Como, Italy. Gastrointest Endosc 2003 Mar;57(3):329-35. Ed: Of course, there are many non-narcotic pain medications which can also be used. Midazolam is a benzodiazepine anti-anxiety medication. Adding acetaminophen would very likely have done just as well and an NSAID would very likely have done better.

Dysmenorrhea: Ibuprofen Better Pain Relief than Narcotic Propoxyphene: In a DB crossover study of 55 women with painful periods over 3 successive cycles, ibuprofen 400 mg was clearly superior to propoxyphene 64 mg or placebo. It gave better relief, had higher patient satisfaction, and less need for additional pain medications with significantly more women able to continue their normal daily functions. Morrison JC, et al. South Med J 1980;73:999-1002.

Dysmenorrhea: Ibuprofen Much More Effective than Propoxyphene: :In a DB crossover study of just 22 patients with severe primary dysmenorrhea, ibuprofen was much more effects a relieving pain (p<0.001). Propoxyphene was somewhat more effective than placebo (p<0.05). Larkin RM, et al. Obstet Gynecol 1979;54:456-60.

Dysmenorrhea: NSAID Mefenamic Acid Better than Propoxyphene/Acetaminophen for Pain and Nausea: In a DB crossover study of 30 women, mefenamic acid 250 mg did significantly better than dextropropoxyphene 32.5/acetaminophen 325 mg. for both pain as well as faintness, nausea, and constipation. Anderson AB, et al. Lancet 1978;1(8060):345-8.

Emergency Department Pain: NSAID Mefenamic Acid as Good as Narcotic Propoxphene with Fewer Side-Effects: In a DB study of 87 patients coming to the emergency department with various problems with acute pain, mefenamic acid did as well as dextropropoxyphene/acetaminophen with fewer side-effects. Sleet RA, et al. Curr Med Res Opin 1980;7:77-84. 

Emergency Department Post-Injury Pain: No Difference Between Non-Narcotic Mefenamic Acid and Propoxyphene/Acetaminophen: In a DB study of 48 patients with soft-tissue injuries, mefenamic acid 250 mg did equally well as dextropropoxyphene 32.5 mg/acetaminophen 325 up to six tablets per day. Stableforth PG. Curr Med Res Opin 1977;5:189-91.

Emergency Room Pain: Ketorolac as Good as Meperidine with Fewer Side-Effects: In a DB study of 93 patients in the emergency room with acute pain, ketorolac 60 mg IM did as well for pain relief as meperidine. Ketorolac caused much less sedation than did meperidine at one hour (p < 0.005). Additional analgesia was requested by 15% of meperidine patients vs. 10% for ketorolac (p = NS). Side-effects occurred in 38% on meperidine vs. 17% on ketorolac (p = 0.0452). Ketorolac vs meperidine for the management of pain in the emergency department. Koenig KL, et al. Highland Hospital Oakland, CA. Acad Emerg Med 1994 Nov-Dec;1(6):544-9.

Fibromyalgia Pain: Morphine Inferior to Ketamine: In a DB PC study of 31 patients with fibromyalgia, morphine did not show any significant changes. Lidocaine showed a pain decrease during and after the infusion. Ketamine showed a significant reduction in pain intensity during and after the test period. Tenderness at tender points decreased and endurance increased significantly, while muscle strength remained unchanged. The present results support the hypothesis that the NMDA receptors are involved in pain mechanisms in fibromyalgia. These findings also suggest that central sensitization is present in FM and that tender points represent secondary hyperalgesia. Pain analysis in patients with fibromyalgia. Effects of intravenous morphine, lidocaine, and ketamine. Sorensen J, et al. University Hospital, Linkoping, Sweden. Scand J Rheumatol. 1995;24(6):360-5.

General Practice Pain Patients: Narcotics Pentazocine and Dihydrocodeine Both Inferior to Acetaminophen; NSAID Floctafenine Best: In a DB PC study of 312 patients suffering from painful conditions, floctafenine was significantly superior in effect to pentazocine but not to the other three agents as far as doctor ratings were concerned; and superior to both pentazocine and dihydrocodeine in the opinion of patients. Fewer patients experienced side-effects on floctafenine than on the other four analgesics and this difference between floctafenine and pentazocine, and floctafenine and dihydrocodeine was statistically significant. A double-blind comparative clinical trial of floctafenine and four other analgesics conducted in general practice. Lomas DM, Gay J, Midha RN, Postlethwaite DL. J Int Med Res. 1976;4(3):179-82.

Labor Pains: Narcotics Ineffective and Unethical: In a DB study of 10 healthy nulliparous women in active labour, even after repeated doses (up to 0.15 mg/kg body weight morphine and up to 1.5 mg/kg body weight meperidine) the findings were uniform, with very high pain scores maintained in each group as assessed with visual analogue scale. The parturients were all significantly sedated and several fell asleep but were awakened by pain during contractions. It was concluded that labor pain is not sensitive to systemically administered morphine or pethidine. These drugs only cause heavy sedation. Authors state, " It therefore seems unethical and medically incorrect to meet parturients' requests for pain relief by giving them sedation. Considering the well documented negative effects on newborn infants we also believe systemic meperidine should be avoided in labor." Lack of analgesic effect of systemically administered morphine or pethidine on labour pain. Olofsson C, et al. Karolinska Hospital, Stockholm, Sweden. Br J Obstet Gynec 1996 Oct;103(10):968-72.

Labor Pains: Meperidine No Better than Placebo for Delivery Pain, But More Side-Effects: In a DB study of 84 women in delivery, there were no statistically significant differences in pain between meperidine and normal saline. Sedative scores, nausea/vomiting and dizziness were significantly worse with meperidine. However, opinion on the effectiveness of pain relief during labor was only 24% in the meperidine group, although it was significantly worse with placebo (7%). Effectiveness of intravenous meperidine for pain relief in the first stage of labour. Soontrapa S, et al. Khon Kaen University, Thailand. J Med Assoc Thai 2002 Nov;85(11):1169-75. Ed: It is virtually certain that using a real pain medication and not a narcotic would have resulted in less pain, fewer side-effects, and lowered the addictive programming of other the mothers and their newborns. One study has shown that children exposed to narcotics during delivery were more likely to develop narcotic programs in adulthood.

Labor Pains: Bupivacaine Equal Pain Relief, Fewer Side-Effect, and Most Satisfaction: In a DB study of 90 mothers with term, uncomplicated pregnancies comparing intermittent bolus epidural analgesia (bupivacaine + fentanyl), patient-controlled epidural analgesia (bupivacaine + fentanyl), or patient-controlled epidural analgesia (bupivacaine), the intermittent bolus epidural analgesia group felt they could influence labor most (p = 0.03), and in the interview they expressed most satisfaction. In this group, the total drug utilization was smallest (bupivacaine: p <0.0001 comparing all groups, fentanyl: p = 0.03 comparing the two fentanyl-receiving groups). No differences in pain occurred. Vomiting (p = 0.04) and pruritus (p <0.0001) were more common or more severe in the groups receiving fentanyl. Patient-controlled epidural analgesia in labor does not always improve maternal satisfaction. Nikkola E, et al. Turku University, Finland. . Acta Obstet Gyn Sand 2006;85(2):188-94. (loss)

Epidural in Labor: Fentanyl Not Needed; High Dose Harms Newborn, Reduces Successful Breastfeeding: In a DB study of 177 women who previously breast-fed a child and who requested labor epidural analgesia, the children of those in the no fentanyl group did non-significantly better than the intermediate-dose fentanyl group (intent to administer between 1 and 150 mug epidural fentanyl) and significantly better than the high-dose epidural fentanyl group (intent to administer > 150 mug epidural fentanyl). Mothers is the high-dose fentanyl reported more difficulty breast-feeding (21%) than women who were randomly assigned to receive an intermediate fentanyl dose (10%), or no fentanyl (10%)(P = 0.09). Neurobehavior scores were lowest in the infants of women who were randomly assigned to receive more than 150 mug fentanyl (P = 0.03). At 6 weeks postpartum, more high-dose epidural fentanyl women were not breast-feeding (17%) than women who were randomly assigned to receive either an intermediate fentanyl dose (5%) or no fentanyl (2%) (P = 0.005). Effect of Labor Epidural Analgesia with and without Fentanyl on Infant Breast-feeding: A Prospective, Randomized, Double-blind Study. Beilin Y, et al. Anesthesiol 2005 Dec;103(6):1211-1217. (loss)

Labor Pains: Sufentanil Added No Benefit to Bupivacaine: In a DB study of 40 women in labor using a combined spinal-epidural technique, intrathecal sufentanil 10 mcg did no better than 12 ml of 0.25% epidural bupivacaine. Pham LH, et al. Harvard. J Clin Anesth 1996;8:497-501. 

Labor and Delivery: Nalbuphine and Butorphanol Caused Infants Not to Initiate Breast-Feeding as Readily: Compared to 22 mothers who did not have labor analgesia, infants whose mothers received analgesia more than one hour before birth initiated breast feeding later, and establied effective feeding significantly later. Crowell MK, et al. Univ of Illinois at Chicago. J Nurse Midwifery 1994;39:150-6. 

Limb Injury: Ketorolac Better Pain Relief than Morphine at Lower Cost, Faster and Fewer Side-Effects: In a study of 148 adults with painful isolated limb injuries, no difference was found in the median time taken to achieve pain relief at rest between the group receiving IV ketorolac and the group receiving IV morphine, but with movement the median reduction in pain score in the ketorolac group was 1.09 per hour compared with 0.87 in the morphine group (P=0.003). The odds of experiencing adverse events was 144 times more likely with morphine than with ketorolac. The median time from the initial delivery of analgesia to the participant leaving the department was 20 minutes shorter in the ketorolac group than in the morphine group (P=0.02). The mean cost per person was $44 in the ketorolac group vs. $229 in the morphine group (P<0.0001). The median score for patients' satisfaction was 6.0 for ketorolac and 5.0 for morphine (P<0.0001). Cost effectiveness analysis of intravenous ketorolac and morphine for treating pain after limb injury: double blind randomised controlled trial. Rainer TH, et al. Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong. BMJ. 2000 Nov 18;321(7271):1247-51.

Musculoskeletal Pain: Oxycodone with Acetaminophen (Percocet) a Little Worse than Valdecoxib (Bextra) for Acute Pain: In a small 51-patient DB study with no placebo control, the COX-2 inhibitor, oral valdecoxib 40 mg did non-significantly better than an oxycodone(10 mg)-acetaminophen(650 mg) combination for acute musculoskeletal pain seen in the emergency department (p = 0.32). Patients treated with valdecoxib were less likely to experience sedation/dizziness (15% vs. 44%, p = 0.03) and to require rescue medications within the next 24 hours (44% vs. 74%, p = 0.04). Comparison of valdecoxib and an oxycodone-acetaminophen combination for acute musculoskeletal pain in the emergency department: a randomized controlled trial. Lovell SJ, et al. Stony Brook University, NY. Ed: The author is wrong in claiming the oral opioids are potent analgesics.  However, the study is acceptable although it is too small to detect anything other than large differences, and is of no benefit for determining how much pain relief came from the acetaminophen and whether oxycodone was of any benefit at all. Valdecoxib is probably not as good as ibuprofen 400 mg with acetaminophen 500 mg and caffeine. 

Neuropathy: Gabapentin and Morphine Studied in Mild-Moderate Neuropathy Pain: In a poorly designed and small 5-week each DB crossover study of 57 patients with either painful diabetic neuropathy or postherpetic neuralgia, patients received daily active placebo (lorazepam), sustained-release morphine, gabapentin, and a combination of gabapentin and morphine. Only 41 completed the trial. Mean daily pain at a maximal tolerated doses was as follows: 5.72 at baseline, 4.49 with lorazepam, 4.15 with gabapentin, 3.70 with morphine, and 3.06 with the gabapentin-morphine combination (P<0.05 for the combination vs. placebo, gabapentin, and morphine). Total scores on the Short-Form McGill Pain Questionnaire (on a scale from 0 to 45, with higher numbers indicating more severe pain) at a maximal tolerated dose were 14.4 with placebo, 10.7 with gabapentin, 10.7 with morphine, and 7.5 with the gabapentin-morphine combination (P<0.05 for the combination vs. placebo, gabapentin, and morphine). Morphine, gabapentin, or their combination for neuropathic pain. Gilron I, et al. Queen's University, Kingston, Ont, Canada. . N Engl J Med. 2005 Mar 31;352(13):1324-34. Ed: These patients had only mild to moderate pain, i.e. 14 points of pain on a 45 point scale. Mixing two totally different causes of pain is poor research practic.  Why anyone would want to use a highly addictive narcotic for chronic mild to moderate pain in conditions that are likely to last for many years, like diabetic neuropathy, or for short-term conditions like PHN, I simply can't understand.  There are many better non-narcotic treatments for diabetic neuropathy than expensive gabapentin or highly addictive morphine. Thiamine, carnitines, nortriptyline, SSRIs like citalopram (Celexa), and lipoic acid would be better initial choices for diabetic neuropathy before gabapentin.

Neuropathic Peripheral Pain Helped by Carbamazepine But Not by Morphine: In a DB PC study of 43 patients with peripheral neuropathic pain, exclusively pain reduced by spinal cord stimulation (SCS), were switched into a painful state after SCS inactivation. This mode was used to assess the pain-relieving effect of carbamazepine (600 mg/d) or placebo during an SCS-free period of 8 days. In Phase 2, 38 patients received either sustained-release morphine (90 mg/d) or placebo for 8 days. In cases of intolerable pain, the patients were authorized to reactivate their SCS. A delay in pain increase was observed in the CMZ group as compared with placebo (P = 0.038), however, the benefit of morphine was insignificant (P = 0.41). The response of neuropathic pain and pain in complex regional pain syndrome I to carbamazepine and sustained-release morphine in patients pretreated with spinal cord stimulation: a double-blinded randomized study. Harke H, et al. Klinikum Krefeld, Germany. Anesth Analg. 2001 Feb;92(2):488-95. 

Postherpetic Neuralgia: Nortriptyline Almost as Good as Morphine In a DB PC crossover study of 76 patients with postherpetic neuralgia, morphine 91 mg or methadone 15 mg did no better than nortriptyline 89 mg or desipramine 63 mg. Opioids and tricyclics (TCA) reduced pain (1.9 and 1.4) more than placebo (0.2; p < 0.001). The trend favoring opioids over TCA fell short of significance (p = 0.06), and reduction in pain with opioids did not correlate with that following TCA. Treatment with opioids and TCA resulted in greater pain relief (38 and 32%) compared with placebo (11%; p < 0.001). More patients completing all three treatments preferred opioids (54%) than TCA (30%; p = 0.02). Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial. Raja SN, et al. Johns Hopkins. . Neurology. 2002 Oct 8;59(7):1015-21. Ed: Nortriptyline is much preferred over desipramine both because nortriptyline is much better researched for pain relief and has a much higher safety index in overdose. Nortriptyline plus a non-narcotic pain relievers would undoubtedly have been far superior to a narcotic by itself and very likely just as good as the narcotic with a non-narcotic pain reliever.  It borders on medical malpractice to give opiates for PHN, since PHN is a temporary condition, the narcotics are obviously unnecessary, and the narcotics too often lead to serious addiction problems.

Propofol Injection Pain: Lignocaine Better than Meperidine: In a DB study of 150 patients receiving propofol, meperidine 25 mg was not as effective as lignocaine 10 mg at reducing pain on injection of propofol. Both active treatments were significantly better than placebo (p < 0.01). A comparison of pethidine and lignocaine. Lyons B, et al. Cappagh Orthopaedic Hospital, Dublin, Ireland. Anesth 1996 Apr;51(4):394-5.

Propofol Injection Pain: Lidocaine as Good as Meperidine with Fewer Side-Effects; Morphine, Fentanyl Inferior: In a DB PC study comparing I.V. pretreatment with fentanyl 150 microg, morphine 4 mg, meperidine 40 mg, 2% lidocaine 3 mL or placebo in reducing propofol injection pain in 175 patients, lidocaine and meperidine significantly reduced propofol injection pain more than placebo (P < 0.05), but there were more side effects in the meperidine group. Fentanyl and morphine reduced the intensity of propofol injection pain (P < 0.05) and had some effect in reducing the incidence of propofol injection pain, but the difference did not reach statistical significance. The analgesic effect of fentanyl, morphine, meperidine, and lidocaine in the peripheral veins: a comparative study. Pang WW, et al. Show-Chwan Memorial Hospital, Changhua, Taiwan. Anesth Analg 1998 Feb;86(2):382-6.

Sprains and Strains: Diflunisal did as Well as Propoxyphene/Acetaminophen: In a 3-day DB study of 51 patients, there was no difference in pain relief or frequency of side-effects between NSAID diflunisal 500 mg and dextropropoxyphene 65 mg/acetaminophen 650 mg 3 times a day. Jaffe GV, et al. Curr Med Res Opin 1978;5:584-8.

Non-Narcotics for Chronic Pain

These are just a few articles of note

Ibuprofen, Piroxicam, Naproxen Did Well for Chronic Pain: Efficacy and side effects of non-opioid-analgesics were analyzed in a standardized review of placebo-controlled or double-blind studies. In rheumatoid arthritis, ibuprofen showed the best ratio of effectiveness and side-effects. Naproxen, diclofenac and meloxicam may serve as alternatives. In osteoarthritis, naproxen seems to be superior to diflunisal, meloxicam and diclofenac. In cancer pain, ibuprofen is the treatment of the first choice followed by naproxen and diclofenac. No sufficient data on non-opioids in neuropathic pain were available. The dose administered in the management of chronic pain should be low in order to reduce the incidence of side-effects. The frequency of side-effect-related discontinuation of chronic pain medication was calculated as follows: ibuprofen 3.8%, aspirin 4.7%, piroxicam 4.8%, naproxen 7.4%, meloxicam 13.0% and diclofenac 17.8%. Since differences in efficacy were not clinically relevant, the indication for a special non-opioid-analgesic medication should focus on the prevention of side-effects. Non-opioid analgesics and co-analgesics in therapy of chronic pain Gehling M, et al Universitatsklinik Freiburg. Z Arztl Fortbild Qualitatssich 1998 Jan;92(1):41-6  

Thomas E. Radecki, M.D., J.D.

modern-psychiatry.com