Pain

On this page, I cover non-narcotic treatments for pain. Opiate pain medications are grossly inferior for pain management and this research is covered in great depth under Opiates.

Non-Opiate Pain Relief Studies

Acetaminophen High Dose as Good as Naprosyn: In a 3-day DB PC crossover study of 95 adults having separate extractions of impacted 3rd molars, naproxen 500 mg x 2 varied from acetaminophen 1000 mg x 4 in minor ways. Summed pain intensity on the day of surgery revealed no statistically significant difference between the acetaminophen or naproxen. At 0.5 hours (p = 0.002) and 1 hour (p = 0.009) after first medication, acetaminophen gave less pain than naproxen. Naproxen was statistically superior (p < or = 0.002) to acetaminophen at 08:00, 12:00, and 16:00 hours on the 1st postoperative day and at 08:00 hours on the 2nd postoperative day, when the pain intensity level was lower than that on the day of surgery. Naproxen 500 mg bid versus acetaminophen 1000 mg qid: effect on swelling and other acute postoperative events after bilateral third molar surgery. Bjornsson GA, et al. University of Oslo, Norway. J Clin Pharmacol. 2003 Aug;43(8):849-58; Similar with ibuprofen 600 mg vs. paracetamol 1000 mg qid in Br J Clin Pharmacol. 2003 Apr;55(4):405-12.

Heated Humidified CO2 Better in Laparoscopy: In a random assignment study of 89 women undergoing laparoscopy, heated 95% humidified CO(2) resulted in significantly less pain in the 48 hours following surgery vs. the standard of heated, dry CO(2). Subgroup analysis in patients without chronic pelvic pain revealed lower mean pain scores at 1, 2, 24, and 48 hours and decreases in postoperative and total morphine equivalents (directional P values < .05) in the study group. Humidified Compared With Dry, Heated Carbon Dioxide at Laparoscopy to Reduce Pain. Beste TM, et al. East Carolina University. Obstet Gyn 2006 Feb;107(2):263-268.

Acetaminophen High Dose Not as Good as Ketoprofen (Toradol) But Difference Minor: In a DB PC crossover study in adults having bilateral "identical" surgical procedures with local anesthesia, a 3-day tablet regime of racemic ketoprofen 75 mg or acetaminophen 1000 mg qid was given starting 3 hours after surgery. Ketoprofen reduced objectively measured swelling 27.8% (p < 0.04) better than acetaminophen 3 days after surgery and 70.8% (p < 0.02) better than acetaminophen 6 days after surgery. The pain intensity (PI) was lower after ketoprofen than after acetaminophen from 2 to 6 hours after the first drug intake (all p-values < or = 0.03). Ketoprofen was a more effective analgesic than acetaminophen only on the day of surgery. There was no difference (p > 0.05) between the treatments with respect to mouth opening, drug preference, global evaluation, or adverse reports. Ketoprofen 75 mg qid versus acetaminophen 1000 mg qid for 3 days on swelling, pain, and other postoperative events after third-molar surgery. Bjornsson GA, et al. University of Oslo, Norway. J Clin Pharmacol. 2003 Mar;43(3):305-14.

Acetaminophen High Dose Not As Good As Soluble Aspirin High Dose in Early Pain: In a DB PC study of 153 adults having extractions of 3rd molars, soluble aspirin 900 mg had more pain relief than paracetamol 1,000 mg during the four hour study when pain is the most intense. There were no significant differences between treatment groups with respect to the number of patients requiring rescue medication, however the time to dosing was significantly longer for those taking soluble aspirin when compared with placebo (p<0.001). An investigation into the comparative efficacy of soluble aspirin and solid paracetamol in postoperative pain after third molar surgery. Seymour RA, et al. University of Newcastle, England. Br Dent J. 2003 Feb 8;194(3):153-7

Acetaminophen Adds to Benefit of Diclofenac: Paracetamol and diclofenac have different mechanisms of action. In a DB study of 60 patients undergoing elective abdominal gynecological surgery, those who received suppositories of paracetamol 1.5 g alone used the most cumulative patient-controlled morphine, diclofenac 100 mg alone was intermediate and the combination of the two was lowest (P < 0.01). Morphine consumption in patients receiving rectal paracetamol and diclofenac alone and in combination. Montgomery JE, et al. Derriford Hospital, Plymouth, USA. Br J Anaesth. 1996 Oct;77(4):445-7. Ed: Diclofenac is available generically for about $.60 per 50 mg. tablet. Ed: This is a poor study since there is no evidence that morphine was needed at all and morphine usage may be a poor measure of pain.

Back Pain: Confirmed key signs and symptoms indicated neuropathic pain was frequent, e.g. radicular pain radiating beyond the knee towards the foot (40.0%), positive Lasegue sign (18.4%), or absent patellar reflex (17.3%). Curr Med Res Opin 2006 Mar;22(3):529-37.

Botulinum toxin (botox) reduces pain after hemorrhoidectomy: results of a double-blind, randomized study:
Davies J, et al. York District Hospital, York, United Kingdom. Dis Colon Rectum. 2003 Aug;46(8):1097-102.

Bupivacaine Lowers Pain After Laparoscopic Inguinal Repair: Laparoscopic preperitoneal inguinal hernia repair is associated with a short hospital stay and an early return to normal activity. In a DB PC study of 44 patients undergoing laparoscopic inguinal hernia repair, those given 80 mg of Bupivacaine in 25 cc of saline installed into the preperitoneal space had better pain relief compared to placebo at 1 hour after surgery (4.0 vs 5.0; p = 0.0038), 2 hours (4.0 vs 5.9; p = 0.0015), and 4 hours (4.3 vs 5.8; p = 0.0038). Preperitoneal bupivacaine attenuates pain following laparoscopic inguinal hernia repair. Bar Dayan A, et al. Sackler School of Medicine, Tel Aviv, Israel. . Surg Endosc. 2004 Jul;18(7):1079-81. Ed: There are many studies with bupivacaine, ropivacaine, and similar drugs showing benefit in reducing pain. Since most involve various surgical procedures, I have not saved them. I thought I would save one to represent the others.

Caffeine Adds to Short-Term Pain Relief of Ibuprofen: In a DB PC study of 161 adults having extractions of 3rd molars, ibuprofen 200 and 400 mg were compared to ibuprofen 200 mg plus 50, 100 or 200 mg of caffeine. There was no significant difference in the effects of 200 and 400 mg of ibuprofen. Adding caffeine to 200 mg ibuprofen produced significantly more analgesic effect at 45 and 60 min than ibuprofen 200 mg alone. Caffeine increased the analgesic effect of ibuprofen 200 mg, through an earlier onset of analgesic effect. Ibuprofen compared with ibuprofen plus caffeine after third molar surgery. McQuay HJ, et al. Oxford, UK. Pain. 1996 Aug;66(2-3):247-51.

Caffeine Adds to Short-Term Pain Relief of Aspirin: In a 6-hour DB PC study of 350 adults having extraction of impacted 3rd molars, single oral dose of aspirin 650 or 1000 mg, caffeine 65 mg, a combination of aspirin 650 mg with caffeine 65 mg, or placebo were compared. All active treatments except caffeine were significantly superior to placebo. Aspirin-caffeine was superior to aspirin 650 mg alone for hours of 50% relief among patients who had severe baseline pain. Adverse effects were transitory and none were serious. Evaluation of aspirin, caffeine, and their combination in postoperative oral surgery pain. Forbes JA, et al. Johns Hopkins. Pharmacotherapy. 1990;10(6):387-93.

Carbamazepine Helps Chronic Trigeminal Neuralgia: Anticonvulsant drugs have been used in the management of chronic neuropathic pain, especially when the pain is lancinating or burning. In a review of 12 DB PC studies including 404 participants, carbamazepine was not effective for acute pain, but was helpful for chronic trigeminal neuralgia patients (4 studies). Carbamazepine for acute and chronic pain. Wiffen P et al. Oxford, UK. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD005451.

Clonidine Intra-Articularly Relieved Post-Op Pain in Arthroscopies: In a DB PC study of 69 patients undergoing knee arthroscopies, those given 150 ug clonidine intra-articularly did better at relieving pain at rest than 150 ug clonidine intravenously or placebo. Intra-articular clonidine has a postoperative analgesic effect after knee arthroscopies due to a peripheral action. Periperal analgesic effect of intra-articularly applied clonidine. Sadjak A, et al. Medizinische Universitat Graz. Schmerz. 2005 Oct 5

Cranial Electrotherapy Stimulation: Spinal Cord Injury Central Pain Helped: Using a very safe technique of non-invasive brain stimulation - transcranial direct current stimulation (tDCS) - on pain control in patients with central pain due to traumatic spinal cord injury, patients were randomized to receive sham or active motor tDCS (2mA, 20min for 5 consecutive days). There was a significant pain improvement after active anodal stimulation of the motor cortex, but not after sham stimulation. These results were not confounded by depression or anxiety changes. Cognitive performance was not significantly changed throughout the trial in both treatment groups. A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. Fregni F, et al. Harvard. Pain 2006 Mar 23.

Cranial Electrotherapy Stimulation: This has a number of more studies reporting benefit. For more, click Here.

Fluoxetine Lessens Effectiveness of Mu-Opiate Morphine: In a 7-day DB PC study of adults having dental surgery, fluoxetine 10 mg daily for 7 day pre-operatively had no effect on pain, but it lessened the pain relief from 6 mg of IV morphine, a mu-opiate, while having no effect on the analgesia produced by the kappa-opiate pentazocine. This effect probably results from alteration in the known serotonergic circuits in endogenous pain-modulating systems. Interactions between fluoxetine and opiate analgesia for postoperative dental pain. Gordon NC, et al. University of California, San Francisco. Pain. 1994 Jul;58(1):85-8. Ed: Most opiates are mu-opiates, i.e., they have their effect on the mu-opiate receptor.

Gene Variant Helps Tolerate Pain: Catechol-O-methyl transferase (COMT) mops up dopamine, which is linked with sensing pain. People with two valine variant genes tolerate pain much better than those with two methionine variant genes and heterozygous in between. 25% of each type with 50% hetero. Jon-Kar Zubieta University of Michigan and NIAA, Rockville. 2/21/03 Science (vol 299, p 1240)

Costs: Acetaminophen 500-1000 mg (generic Tylenol) as cheap as 2 cents per 500 mg; Bextra (withdrawn from the market); Celecoxib (Celebrex) $3.00 per tablet; Diclofenac (generic Voltaren): 65 cents per 50 mg. tablet; Etoricoxib (Arcoxia: not available in U.S., a COX-2 inhibitor); Flurbiprofen 75 cents for a 100 mg tablet which can be broken in half (50 mg tabs are no cheaper); Ibuprofen 200-800 mg: as cheap as 2 cents per 200 mg.); Indomethacin: 30 cents per 50 mg. capsule or $27 per month with TID dosing; Ketorolac (generic Toradol): 90 cents per 10 mg. tablet; Vioxx (withdrawn from the market)

Nerve Block: Very Helpful After Total Knee Replacement: Continuous-infusion femoral nerve block (FNB) improves analgesia and rehabilitation after total knee replacement. In a DB PC study of 30 patients after total knee replacement, a 40-mL injection of 0.25% bupivacaine resulted in lower VAS pain scores (P <.01 in the postoperative anesthesia care unit, P <.05 on the day after surgery), lower total morphine use (P <.05), and a lower incidence of morphine-related side effects. More could ambulate on the day after surgery (93% v 46%, P <.05), and ambulatory distance was better at discharge (166 v 117 feet, P <.01). Knee flexion was also better on the second day after surgery (70 degrees v 60 degrees, P <.01), but the between-group difference was no longer statistically significant at discharge. Length of acute hospitalization was shorter (3 days vs. 4 days average, P <.05). The effect of single-injection femoral nerve block on rehabilitation and length of hospital stay after total knee replacement. Wang H, et al. Henry Ford Hospital, Detroit. . Reg Anesth Pain Med. 2002 Mar-Apr;27(2):139-44. Ed: Many studies find that various nerve blocks are effective at decreasing various types of surgical pain. This study is representative. Of course, there is absolutely no evidence that any opiates were required, since no alternative non-narcotic pain reliever was offered as an alternative. In fact, it is very likely that the opiate would offer inferior pain relief to most non-narcotic pain relievers.

Osteoporosis: Calcitonin SC Reduces Pain: In a 2 week DB PC study of 58 patients with osteoporosis with all on calcium 1000 mg/d, subcutaneously 100 IU salmon calcitonin increased beta-endorphin levels (p<0.001) with more pain relief (p<0.05). The effect of calcitonin on beta-endorphin levels in postmenopausal osteoporotic patients with back pain. Ofluoglu D, et al. Marmara University, Istanbul, Turkey. Clin Rheumatol 2006 Mar 31.

Supermint Oil for C-Section Pain: In a 107-woman DB PC study of pain after caesarean sections, 40 drops of supermint every 20 minutes three times just after serum disconnection significantly reduced pain at second 40 minutes (p<0/002), 60 minutes (p<0/001) and 120 minutes (p<0/001) after intervention. The effect of supermint oil on pain severity after caesarean section. Fazel N. Sabzevar Univ. Asia Pac J Clin Nutr. 2004;13(Suppl):S126

TENS Unit Helped Post-Op Shoulder Pain: In a 3-day DB PC study of 30 patients, those using the real TENS units immediately postoperatively for 8 hours and then on the following days 5 times daily for 45 minutes used significantly less morphine and had significantly less pain. Postoperative transcutaneous electrical nerve stimulation (TENS) in shoulder surgery (randomized, double blind, placebo controlled pilot trial). Likar R, et al. Klagenfurt, Austria. Schmerz. 2001 Jun;15(3):158-63. Ed: This is one of a huge number of studies showing some benefit to TENS units for a wide variety of pain conditions.

Tricylics Better than SSRIs: Review of 59 DB studies. Results with SSRIs are conflicting. Trazodone not beneficial. Venlafaxine and nefazodone not yet available. Antidepressants as analgesics: a review of randomized controlled trials. Lynch ME. J Psychiatry Neurosci 2001 Jan;26(1):30-6

Amitriptyline Better than Trazodone or Desipramine for Arthritis Pain: 47 pt DB PC crossover. Antidepressant analgesia in rheumatoid arthritis. Frank RG, Kashani JH, Parker JC, Beck NC, Brownlee-Duffeck M, Elliott TR, Haut AE, Atwood C, Smith E, Kay DR. J Rheumatol 1988 Nov;15(11):1632-8

COX-2 Inhibitors: Most non-steroidal anti-inflammatory drugs (NSAIDs) block both cyclooxygenase-1 (COX-1) and COX-2. COX-1 produces protective prostagladins while COX-2 produces inflammatory ones. Celebrex and Vioxx were the leading brands of COX-2 inhibitors. They cause less stomach inflammation or ulcers or adverse interactions with blood thinners. Benefits, e.g. against Alzheimers and colon cancer might be similar to NSAIDs. However, Vioxx causes a higher death rate from heart disease and was pulled from the market in November, 2004. The small benefits of Celebrex are outweighed by its high cost.

Clomipramine Better than Nortriptyline: DB PC crossover for cancer-related and other central pain like stump pain & post-herpetic. Clomipramine much better. A randomized, within-patient, cross-over, placebo-controlled trial on the efficacy and tolerability of the tricyclic antidepressants chlorimipramine and nortriptyline in central pain. U Milan: Panerai AE, Monza G, Movilia P, Bianchi M, Francucci BM, Tiengo M. Acta Neurol Scand 1990 Jul;82(1):34-8

Ibuprofen Plus Acetaminophen Best for Acute Pain from Root Canal Surgery: In a 57-patient DB PC study of moderate to severe postoperative root canal treatment pain, a single dose of either: (i) placebo; (ii) 600 mg ibuprofen; or (iii) 600 mg ibuprofen and 1000 mg of acetaminophen found that the combination of ibuprofen and acetaminophen was the most effective and significantly more effective than placebo. The efficacy of pain control following nonsurgical root canal treatment using ibuprofen or a combination of ibuprofen and acetaminophen in a randomized, double-blind, placebo-controlled study. Menhinick KA, Gutmann JL, Regan JD, Taylor SE, Buschang PH. Int Endod J. 2004 Aug;37(8):531-41

Ibuprofen Liquigel Did Slightly Better Than Acetaminophen or Ketoprofen: A solubilized 200 mg liquigel formulation of ibuprofen has been shown to have a more rapid rate of absorption compared with ibuprofen 200 mg tablets. In a DB PC study of 239 adults having extraction of 3rd molars, liquigel ibuprofen 400 mg, had faster onset and less pain over the 6 hour study than ketoprofen 25 mg compared with acetaminophen 1000 mg, and placebo. By the end of the study (6 h), onset of meaningful relief was achieved by 36%, 99%, 96%, and 88% of the patients in the placebo, ketoprofen, ibuprofen, and acetaminophen groups, respectively. The median times to onset of relief were > 6 hours for placebo, 25.5 minutes for ketoprofen, 24.2 minutes for ibuprofen, and 29.9 minutes for acetaminophen. Onset of analgesia for liquigel ibuprofen 400 mg, acetaminophen 1000 mg, ketoprofen 25 mg, and placebo in the treatment of postoperative dental pain. Olson NZ, et al. Analgesic Development, Ltd, New York NY. J Clin Pharmacol. 2001 Nov;41(11):1238-47.

Ibuprofen 600 mg a Little Better than Diclofenac 50 mg: In a 1-week DB PC study of 81 adults with extractions of impacted wisdom teeth, the results with ibuprofen 600 mg. vs. diclofenac 50 mg. every 8 hours were similar in the first 48 postoperative hours in both groups, though on the third day the diclofenac group tended to show higher pain scores (p<0.05). This tendency was also reflected by an increased need for rescue medication and the consumption of a larger number of tablets in the diclofenac group. Analgesic efficacy of diclofenac sodium versus ibuprofen following surgical extraction of impacted lower third molars. Esteller-Martinez V, et al. Universidad de Barcelona, Spain. Med Oral Patol Oral Cir Bucal. 2004 Nov-Dec;9(5):448-53; 444-8.

Diclofenac 100 mg Better than 25 mg or 50 mg: In a DB PC study of 265 adults having removal of impacted wisdom teeth, 100 mg of diclofenac did significantly better for 3 and 6-hour pain relief than 25 mg or 50 mg and these doses did better than placebo. Dose-ranging analgesic study of Prosorb diclofenac potassium in postsurgical dental pain. Hersh EV, et al. University of Pennsylvania. . Clin Ther. 2004 Aug;26(8):1215-27.

High-power Ultrasound Helps Acute Neck Pain: To study what effects a high-power, pain-threshold, static ultrasound technique applied to acute myofascial trigger points of the upper trapezius has on pain and on active cervical lateral bending, researchers did a DB study of 72 adults with acute pain on one side of the neck. High-power ultrasound applied to the trigger points before stretching the muscle was more effective (P<.05) than conventional ultrasound, and it also significantly (P<.001) decreased the length of therapy. Majlesi J, Unalan H. High-power pain threshold ultrasound technique in the treatment of active myofascial trigger points: a randomized, double-blind, case-control study. Arch Phys Med Rehabil 2004;85:833-6.

Dynamic training & Relaxation Training No Help for Neck Pain: 393 women chronic neck pain randomized 12 weeks rx. No diff in pain although lateral ROM increased with training. Effectiveness of dynamic muscle training, relaxation training, or ordinary activity for chronic neck pain: randomised controlled trial. Matti Viljanen, Antti Malmivaara, Jukka Uitti, Marjo Rinne, Pirjo Palmroos, Pekka Laippala BMJ 2003;327:475 (30 August)

Sertraline, Imipramine Help Noncardiac Chest Pain: 30 pt DB PC 8 week study up to 200 sertraline vs. placebo found decrease chest pain 4 to 1.5 with no change BDI. Varia, Amer Heart J 00;140:367. Earlier studies have shown imipramine also of value.

Carbamazepine May Help: Like several tricyclics and lithium, carbamazepine reportedly helps some trigeminal neuralgia, and DM or uremic peripheral neuropathies. An open study of intractable neurogenic pain or post-herpetic neuralgia, 1/3 got considerable relieve from carbamazepine. Scot Med J 84;29:162

Amitriptyline Helps More Patients Than Carbamazepine for Post-Stroke Pain: 15 pt DB 4 weeks then 1 week washout then 4 week crossover. 10 of 15 helped by amitriptyline 75mg/d starting 2^nd week. 5 of 15 helped by carbamazepine 800mg/d. Amitrip-nortrip total blood levels in responders 497 vs. 247 and non-responders. Central post-stroke pain--a controlled trial of amitriptyline and carbamazepine. Leijon G, Boivie J.

Bupropion Helps Neuropathic Pain in DB: DB PC 41 pt 6 week crossover 30% decr pain with bupropion and no impact placebo. Double-blind, randomized trial of bupropion SR for the treatment of neuropathic pain. Semenchuk MR, Sherman S, Davis B. Neurology 2001 Nov 13;57(9):1583-8

Rofecoxib No Better Than Ibuprofen; Just Longer Acting: In a 24-hour DB PC study of 151 adults having 3rd molar extractions, a single dose of placebo, rofecoxib 50 mg, or ibuprofen 400 mg were compared. Rofecoxib 50 mg was more effective than placebo, but its overall analgesic effects, onset of analgesia, and peak analgesic effects that were not significantly different from those of ibuprofen 400 mg, with a significantly longer duration of action (P < 0.05). Analgesic efficacy of the cyclooxygenase-2-specific inhibitor rofecoxib in post-dental surgery pain: a randomized, controlled trial. Morrison BW, et al. Merck Research Laboratories. Clin Ther. 1999 Jun;21(6):943-53.

Snail Venom Drug Relieves Intent Chronic Pain: Ziconotide, a drug from the venom of a small snail from Utah, selectively blocks N-type voltage-sensitive calcium channels. In a DB PC study at 32 cancer centers, 111 adults with intractable AIDS or cancer pain despite daily morphine or other opiates, intrathecal ziconotide titrated over 5 days, followed by a 5-day maintenance phase for responders and crossover of nonresponders to the opposite treatment group found improved pain control of 53% with ziconotide vs. 18% with placebo (P<.001), with no loss of efficacy of ziconotide in maintenance. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. Staats PS, Yearwood T, et al. Johns Hopkins. JAMA. 2004 Jan 7;291(1):63-70.

Venlafaxine Reduced Postmastectomy Pain: Postmastectomy pain syndrome (PMPS) is a neuropathic pain syndrome that may develop following breast surgery. In a 2-week DB PC study starting the night before surgery to 100 patients for either partial or radical mastectomy with axillary dissection, patients were all administered PCA morphine for the first 24 hours following surgery and then acetaminophen/oxycodone tablets. There was no difference in postoperative opioid use between the venlafaxine and placebo groups. Pain scores with movement were lower in the venlafaxine group at 6 months. Pain scores at all other time intervals were similar. There was a significant decrease in the incidence of chest wall pain (55% vs. 19%, P = 0.0002), arm pain (45% vs. 17%, P = 0.003), and axilla pain (51% vs. 19%, P = 0.0009) between the control group and the venlafaxine group. Evaluation of efficacy of the perioperative administration of venlafaxine XR in the prevention of postmastectomy pain syndrome. Reuben SS, et al. Baystate Medical Center, Springfield, MA. J Pain Symptom Manage. 2004 Feb;27(2):133-9.