1Verdu, E, Ceballos, D, Vilches, JJ, Navarro, X. Influence of aging on peripheral nerve function and regeneration. J Peripher Nerv Syst 2000; 5: 191–208.
2Bergman, E, Johnson, H, Xhang, X, Hokfelt, T, Ulfhake, B. Neuropeptides and neurotrophin receptor mRNAs in primary sensory neurons of aged rats. J Comp Neurol 1996; 11: 303–19.
3Wong, DF, Wagner, HN, Dannals, RF. Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain. Science 1984; 226: 1393–96.
4Laporte, AM, Doyen, C, Nevo, IT. Autoradiographic mapping of serotonin 5HT1A, 5HT1D, 5HT2A and 5HT3 receptors in the aged human spinal cord. J Chem Neuroanat 1996; 11: 67–75.
5Barili, P, De Carolis, G, Zaccheo, D, Amenta, F. Sensitivity to ageing of the limbic dopaminergic system: a review. Mech Ageing Dev 1998; 106: 57–92.
6Pakkenberg, B, Gundersen, HJ. Neocortical neuron number in humans: effect of sex and age. J Comp Neurol 1997; 384: 312–20.
7Kim, KJ, Moriyama, K, Han, KR, Sharma, M, Han, X, Xie, GX, Palmer, PP. Differential expression of the regulator of G protein signalling RGS9 protein in nociceptive pathways of different age rats. Brain Res Dev 2005; 160: 28–39.
8Finkel, JC, Besch, VG, Hergen, A, Kakareka, J, Pohida, T, Melzer, JM, Koziol, D, Wesley, R, Quezado, ZM. Effects of aging on current vocalization threshold in mice measured by a novel nociceptive assay. Anesthesiology 2006; 105: 360–69.
9Gagliese, L, Melzack, R. Neurosci Biobehav Rev 2000; 24: 843–54.
10Jourdan, D, Boghossian, S, Alloui, A, Veyrat-Durebex, C, Coudore, MA, Eschalier, A, Alliot, J. Age-related changes in nociception and effect of morphine in the Lou rat. Eur J Pain 2000; 4: 291–300.
11Cruce, WL, Lovell, JA, Crisp, T, Stuesse, SL. Effect of aging on the substance P receptor, NK-1, in the spinal cord in rats with peripheral nerve injury. Somatosens Mot Res 2001; 18: 66–75.
12Ririe, DG, Vernon, TL, Tobin, JR, Eisenach, JC. Age dependent responses to thermal hyperalgesia and mechanical allodynia in a rat model of acute postoperative pain. Anesthesiology 2003; 99: 443–48.
13Gagliese, L, Melzack, R. Age differences in the response to the formalin test in rats. Neurobiol Aging 1999; 20: 699–707.
14Onodera, K, Sakurada, S, Furuta, S, Yonezawa, A, Hayashi, T, Honma, I, Miyazaki, S. Age-related differences in forced walking stress-induced analgesia in mice. Drugs Exp Clin Res 2001; 27: 193–98.
15Iwata, K, Fukuoka, T, Kondo, E, Tsuboi, Y, Tashiro, A, Noguchi, K, Masuda, Y, Morimoto, T, Kanda, K. Plastic changes in nociceptive transmission of the rat spinal cord with advancing age. J Neurophysiol 2002; 10: 1086–93.
16Wang, Y, Mitchell, J, Moriyama, K, Kim, KJ, Sharma, M, Xie, GX, Palmer, PP. Age-dependent morphine tolerance development in the rat. Anesth Analg 2005; 100: 1733–39.
17Sternberg, WF, Ritchie, J, Mogil, JS. Qualitative sex differences in kappa-opioid analgesia in mice are dependent on age. Neurosci Lett 2004; 363: 178–81.
18Gibson, SJ. Pain and aging: the pain experience over the adult lifespan. In Proceedings of the 10th World Congress on Pain, IASP Press, Seattle, 2003.
19Zheng, Z, Gibson, SJ, Khalil, Z, Helme, RD, McMeekin, JM. Age related differences in the time course of capsaicin induced hyperalgesia. Pain 2000; 85: 51–58.
20Lasch, H, Castell, DO, Castell, JA. Evidence for diminished visceral pain with aging: studies using graded intraesophageal balloon distension. Am J Physiol 1997; 272: G1–3.
21Gibson, SJ, Voukelatos, X, Ames, D, Flicker, L, Helme, RD. An examination of pain perception and cerebral event related potentials following carbon dioxide laser stimulation in patients with Alzheimer's disease and age-matched control volunteers. Pain Res Manag 2001; 6: 126–32.
22Harkins, SW. Effects of aged and interstimulus interval on the brainstem auditory evoked potential. Int J Neurosci 1981; 15: 107–18.
23Lautenbacher, S, Kunz, M, Strate, P, Nielsen, J, Arendt-Nielsen, L. Age effects on pain thresholds, temporal summation and spatial summation of heat and pressure pain. Pain 2005; 115: 410–18.
24Edwards, RR, Fillingham, RB, Ness, TJ. Age-related differences in endogenous pain modulation: a comparison of diffuse noxious inhibitory controls in healthy older and younger adults. Pain 2003; 101: 155–65.
25Yunis, MB, Holt, GS, Masi, AT, Aldag, JC. Fibromyalgia syndrome among the elderly. Comparisons with younger patients. J Am Geriatr Soc 1988; 36: 987–95.
26Brattberg, G, Parker, MG, Thorslund, M. The prevalence of pain among the oldest in Sweden. Pain 1996; 67: 29–34.
27Reyes-Gibby, CC, Aday, LA, Todd, KH, Cleeland, CS, Anderson, KO. Pain in aging community-dwelling adults in the United States: non-Hispanic whites, non-Hispanic blacks, and Hispanics. J Pain 2007; 8: 75–84.
28Bressler, HB, Keyes, WJ, Rochon, PA, Badley, E. The prevalence of low back pain in the elderly. A systematic review of the literature. Spine 1999; 24: 1813–19.
29Dionne, CE, Dunn, KM, Croft, PR. Does back pain prevalence really decrease with increasing age? A systematic review. Age Ageing 2006; 35: 229–34.
30Salaffi, F, Carotti, M, Stancati, A, Grassi, W. Health-related quality of life in older adults with symptomatic hip and knee osteoarthritis: a comparison with matched healthy controls. Aging Clin Exp Res 2005; 17: 253–54.
31Buntin-Mushock, C, Phillip, L, Moriyama, K, Palmer, PP. Age-dependent opioid escalation in chronic pain patients. Anesth Analg 2005; 100: 1740–45.
32Scherder, EJ, Bouma, A. Is decreased use of analgesics in Alzheimer disease due to change in the affective component of pain? Alzheimer Dis Assoc Disord 1997; 11: 171–74.
33Pickering, G, Jourdan, D, Dubray, C. Acute versus chronic pain treatment in Alzheimer's disease. Eur J Pain 2006; 10: 379–84.
34Scherder, EJ, Slaets, J, Deijen, JB, Gorter, Y, Ooms, ME, Ribbe, M, Vuijk, PJ, Feldt, K, van de Valk, M, Bouma, A, Sergeant, JA. Pain assessment in patients with possible vascular dementia. Psychiatry 2003; 66: 133–45.
35Cornali, C, Franzoni, S, Gatti, S, Trabucchi, M. Diagnosis of chronic pain caused by osteoarthritis and prescription of analgesics in patients with cognitive impairment. J Am Med Dir Assoc 2006; 7: 1–5.
36Davies, PS, Galer, BS. Review of lidocaine 5% patch studies in the treatment of postherpetic neuralgia. Drugs 2004; 64: 937–47.
37Gammaitoni, AR, Davis, MW. Pharmacokinetics and tolerability of lidocaine 5% patch with extended dosing. Ann Pharmacother 2002; 36: 236–40.
38Habib, AS, Polascik, TJ, Weizer, AZ, White, WD, Moul, JW, ElGasim, MA, Gan, TJ. Lidocaine patch for postoperative analgesia after radical retropubic prostatectomy. Anesth Analg 2009; 108: 1950–53. This is the first study to confirm the clinical impression that topical application of lidocaine patch reduces post-operative pain.
39Saber, AA, Elgamal, AH, Rao, AJ et al. Early experience with lidocaine patch for postoperative pain control after laparoscopic ventral hernia repair. Int J Surg 2009; 7: 36–38.
40Affaitati, G, Fabrizio, A, Savini, A, Lerza, R, Tafuri, E, Costantini, R, Lapenna, D, Giamberardino, MA. A randomized, controlled study comparing a lidocaine patch, a placebo patch, and anaesthetic injection for treatment of trigger points in patients with myofascial pain syndrome: evaluation of pain and somatic pain thresholds. Clin Ther 2009; 31: 705–20.
41Gimbel, J, Linn, R, Hale, M, Nicholson, B. Lidocaine patch treatment in patients with low back pain: results of an open-label, non-randomized pilot study. Am J Ther 2005; 12: 311–19.
42Gammaitoni, AR, Galer, BS, Onawola, R, Jensen, MP, Argoff, CE. Lidocaine patch 5% and its positive impact on pain qualities in osteoarthritis: results of a pilot 2-week open label study using the Neuropathic Pain Scale. Curr Med Res Opin 2004; 20: S13–19.
43Duarte, ID, Lorenzetti, BB, Ferreira, SH. Acetylcholine induces peripheral analgesia by the release of nitric oxide. In Moncada, S, Higgs, A (eds), Nitric Oxide from L-Arginine. A Bioregulatory System. Elsevier, Amsterdam, 1990; pp. 165–70.
44Feelisch, M, Noack, EA. Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase. Eur J Pharmacol 1987; 139: 19–30.
45Knowles, RG, Palacios, M, Palmer, RM, Moncada, S. Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase. Proc Natl Acad Sci USA 1989; 86: 5159–62.
46Berrazueta, JR, Fleitas, M, Salas, E, Amado, JA, Poveda, JJ, Ochoteco, A, Sánchez de Vega, MJ, Ruiz de Celis, G. Local transdermal glyceryl trinitrate has an anti-inflammatory action on thrombophlebitis induced by sclerosis of leg varicose veins. Angiology 1994; 45: 347–51.
47Berrazueta, JR, Losada, A, Poveda, J, Ochoteco, A, Riestra, A, Salas, E, Amado, JA. Successful treatment of shoulder pain syndrome due to supraspinatus tendonitis with transdermal nitroglycerin. A double blind study. Pain 1996; 66: 63–67.
48Paoloni, JA, Appleyard, RC, Nelson, J, Murrell, GA. Topical nitric oxide application in the treatment of chronic extensor tendinosis at the elbow: a randomized, double-blind, placebo-controlled clinical trial. Am J Sports Med 2003; 31: 915–20.
49Paoloni, JA, Appleyard, RC, Nelson, J, Murrell, GA. Topical glyceryl trinitrate treatment of chronic non-insertional Achilles tendinopathy. A randomized, double-blind, placebo-controlled trial. J Bone Joint Surg Am 2004; 86: 916–22.
50Paoloni, JA, Appleyard, RC, Nelson, J, Murrell, GA. Topical glyceryl trinitrate application in the treatment of chronic supraspinatus tendinopathy: a randomized, double-blinded, placebo-controlled clinical trial. Am J Sports Med 2005; 33: 806–13.
51McCleane, GJ, McLaughlin, M. The addition of GTN to capsaicin cream reduces the discomfort associated with application of capsaicin alone. Pain 1998; 78: 149–52.
52Walker, RJ, McCleane, GJ. The addition of glyceryl trinitrate to capsaicin cream reduces the thermal allodynia associated with the application of capsaicin alone in humans. Neurosci Lett 2002; 323: 78–80.
53McCleane, GJ. The analgesic efficacy of topical capsaicin is enhanced by glyceryl trinitrate in painful osteoarthritis: a randomized, double-blind, placebo controlled study. Eur J Pain 2000; 4: 355–60.
54Dong, X-D, Svensson, P, Cairns, BE. The analgesic action of topical diclofenac may be mediated through peripheral NMDA receptor antagonism. Pain 2009; 147: 36–45. This study shows an additional peripheral mode of action of the NSAID diclofenac.
55Cairns, BE, Svensson, P, Wang, K, Hupfeld, S, Graven-Nielsen, T, Sessle, BJ, Berde, CB, Arendt-Nielsen, L. Activation of peripheral NMDA receptors contributes to human pain and rat afferent discharges evoked by injection of glutamate into the masseter muscle. J Neurophysiol 2003; 90: 2098–105.
56Cairns, BE, Dong, XD. The role of peripheral glutamate and glutamate receptors in muscle pain. J Musculoskeletal Pain 2008; 16: 85–91.
57Alves, DP, Tatsuo, MA, Leite, R, Duarte, ID. Diclofenac-induced peripheral antinociception is associated with ATP-sensitive K+ channels activation. Life Sci 2004; 74: 2577–91.
58Ortiz, MI, Torres-López, JE, Castañeda-Hernández, G, Rosas, R, Vidal-Cantú, GC, Granados-Soto, V. Pharmacological evidence for the activation of K (+) channels by diclofenac. Eur J Pharmacol 2002; 438: 85–91.
59Vestergaard, P, Rejnmark, L, Mosekilde, L. Fracture risk associated with the use of morphine and opiates. J Intern Med 2006; 260: 76–87.
60Lunn, MP, Hughes, RA, Wiffen, PJ. Duloxetine for treating painful neuropathy or chronic pain. Cochrane Database Syst Rev 2009; 4: CD007115.
61Arnold, LW, Clauw, DJ, Wohlreich, MM et al. Efficacy of duloxetine in patients with fibromyalgia: pooled analysis of 4 placebo-controlled clinical trials. Prim Care Companion J Clin Psychiatry 2009; 11: 237–44.
62Harder, A, Gerner, P, Kao, G et al. Cutaneous analgesia after transdermal application of amitriptyline versus lidocaine in rats. Anesth Analg 2003; 96: 1707–10.
63Esser, MJ, Sawynok, J. Acute amitriptyline in a rat model of neuropathic pain: differential symptom and route effects. Pain 1999; 80: 643–53.
64Esser, MJ, Chase, T, Allen, GV, Sawynok, J. Chronic administration of amitriptyline and caffeine in a rat model of neuropathic pain: multiple interactions. Eur J Pharmacol 2001; 430: 211–18.
65Sawynok, J, Esser, MJ, Reid, AR. Peripheral antinociceptive actions of desipramine and fluoxetine in an inflammatory and neuropathic pain test in the rat. Pain 1999; 82: 149–58.
66Sawynok, J, Reid, AR, Esser, MJ. Peripheral antinociceptive action of amitriptyline in the rat formalin test: involvement of adenosine. Pain 1999; 80: 45–55.
67Sawynok, J, Reid, A. Peripheral interactions between dextromethorphan, ketamine and amitriptyline on formalin-evoked behaviours and paw edema in rats. Pain 2003; 102: 179–86.
68Heughan, CE, Allen, GV, Chase, TD, Sawynok, J. Peripheral amitriptyline suppresses formalin-induced Fos expression in the rat spinal cord. Anesth Analg 2002; 94: 427–31.
69McCleane, GJ. Topical doxepin hydrochloride reduces neuropathic pain: a randomized, double-blind, placebo controlled study. The Pain Clinic 1999; 12: 47–50.
70McCleane, GJ. Topical administration of doxepin hydrochloride, capsaicin and a combination of both produces analgesia in chronic human neuropathic pain: a randomised, double-blind, placebo-controlled study. Br J Clin Pharmacol 2000; 49: 574–79.
71McCleane, GJ. Topical application of doxepin hydrochloride can reduce the symptoms of complex regional pain syndrome: a case report. Injury 2002; 33: 88–89.
72Epstein, JB, Truelove, EL, Oien, H, Allison, C, Le, ND, Epstein, MS. Oral topical doxepin rinse: analgesic effect in patients with oral mucosal pain due to cancer or cancer therapy. Oral Oncol 2001; 37: 632–37.
73Rowbotham, MC, Davies, PS, Verkempinck, C, Galer, BS. Lidocaine patch: double-blind controlled study of a new treatment method for post-herpetic neuralgia. Pain 1996; 65: 39–44.
74Galer, BS, Rowbotham, MC, Perander, J, Friedman, E. Topical lidocaine patch relieves post-herpetic neuralgia more effectively than vehicle patch: results of an enriched enrolment study. Pain 1999; 80: 533–38.
75Herrmann, DN, Barbano, RL, Hart-Gouleau, S, Pennella-Vaughan, J, Dworkin, RH. An open-label study of the lidocaine patch 5% in painful idiopathic sensory polyneuropathy. Pain Med 2005; 6: 379–84.
76Scarpini, E, Sacilotto, G, Baron, P, Cusini, M, Scarlato, G. Effect of acetyl-L-carnitine in the treatment of painful peripheral neuropathies in HIV+ patients. J Peripher Nerv Syst 1997; 2: 250–52.
77Sima, AA, Calvani, M, Mehra, M, Amato, A. Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy. Diabetes Care 2005; 28: 96–101.
78Flatters, SJ, Xiao, WH, Bennett, GJ. Acetyl-L-carnitine prevents and reduces paclitaxel-induced painful peripheral neuropathy. Neurosci Lett 2006; 397: 219–23.
79Ghirardi, O, Lo Giudice, P, Pisano, C, Vertechy, M, Bellucci, A, Vesci, L, Cundari, S, Miloso, M, Rigamonti, LM, Nicolini, G, Zanna, C, Carminati, P. Acetyl-L-carnitine prevents and reverts experimental chronic neurotoxicity induced by oxaliplatin, without altering its antitumor properties. Anticancer Res 2005; 25: 2681–87.
80Ghirardi, O, Vertechy, M, Vesci, L, Canta, A, Nicolini, G, Galbiati, S, Ciogli, C, Quattrini, G, Pisano, C, Cundari, S, Rigamonti, LM. Chemotherapy-induced allodynia: neuroprotective effect of acetyl-L-carnitine. In Vivo 2005; 19: 631–37.
81Hart, AM, Wilson, AD, Montovani, C, Smith, C, Johnson, M, Terenghi, G, Youle, M. Acetyl-L-carnitine: a pathogenesis based treatment for HIV-associated antiretroviral toxic neuropathy. AIDS 2004; 18: 1549–60.
82Herzmann, C, Johnson, MA, Youle, M. Long-term effect of acetyl-L-carnitine for antiretroviral toxic neuropathy. HIV Clin Trials 2005; 6: 344–50.
83Chiechio, S, Caricasole, A, Barletta, E, Storto, M, Catania, MV, Copani, A, Vertechy, M, Nicolai, R, Calvani, M, Melchiorri, D, Nicoletti, F. L-acetylcarnitine induces analgesia by selectively up-regulating mGlu2 metabotropic glutamate receptors. Mol Pharmacol 2002; 61: 989–96.
84Chiechio, S, Copani, A, De Petris, L, Morales, ME, Nicoletti, F, Gereau, RW 4th. Transcriptional regulation of metabotropic glutamate receptor 2/3 expression by the NF-kappaB pathway in primary dorsal root ganglia neurons: a possible mechanism for the analgesic effect of L-acetylcarnitine. Mol Pain 2006; 2: 20.
85Yu, XH, Zhang, ET, Craig, AD, Shigemoto, R, Ribeiro-da-Silva, A, De Koninck, Y. NK-1 receptor immunoreactivity in distinct morphological types of lamina 1 neurons of the primate spinal cord. J Neurosci 1999; 19: 3545–55.
86Hunt, S, Mantyh, P. The molecular dynamics of pain control. Nature Reviews 2001; 2: 83–91.
87Marshall, G, Shehab, S, Spike, R, Todd, A. Neurokinin-1 receptors on lumbar spinothalamic neurons in the rat. Neuroscience 1996; 72: 255–63.
88Muller, W, Fiebich, BL, Stratz, T. New treatment options using 5HT3 receptor antagonists in rheumatic diseases. Curr Top Med Chem 2006; 6: 2035–42.
89Stratz, T, Farber, L, Varga, B, Baumgartner, C, Haus, U, Muller, W. Fibromyalgia treatment with intravenous tropisetron. Drugs Exp Clin Res 2001; 27: 113–18.
90Tolk, J, Kohnen, R, Muller, W. Intravenous treatment of fibromyalgia with the 5HT3 receptor antagonist tropisetron in a rheumatological practice. Scand J Rheumatol Suppl 2004; 119: 72–75.
91McCleane, GJ, Suzuki, R, Dickenson, AH. Does a single intravenous injection of the 5HT3 receptor antagonist ondansetron have an analgesic effect in neuropathic pain? A double-blind, placebo-controlled cross-over study. Anesth Analg 2003; 97: 1474–78.
92Miranda, A, Peles, S, McLean, PG, Sengupta, JN. Effects of the 5HT3 receptor antagonist, alosetron, in a rat model of somatic and visceral hyperalgesia. Pain 2006; 126: 54–63.