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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Analgesia

  • Although substance P did not mediate the signalling of acute pain or hyperalgesia, it was essential for the full development of stress-induced analgesia and for an aggressive response to territorial challenge, demonstrating that the peptide plays an unexpected role in the adaptive response to stress [1].
  • NT-induced analgesia and hypothermia both were significantly dose-dependent [2].
  • These results demonstrate that CCK-B receptors are expressed by a substantial percentage of dorsal root ganglion neurons at all spinal levels, and that CCK may antagonize opiate analgesia at the level of the primary afferent neuron itself [3].
  • A single-blind (n = 1) study to confirm analgesia was completed by administration of aspartame to A.B.E. A controlled double-blind trial was performed in patients with x-ray-documented osteoarthritis [4].
  • In order to assess the analgesia obtained from single oral doses of paracetamol alone and in combination with codeine in postoperative pain, we conducted a systematic review of randomised controlled trials [5].

Psychiatry related information on Analgesia

  • Because our previous studies of MOR-deficient mice have shown that this receptor protein is also responsible for morphine analgesia, reward, and physical dependence, the present results imply that MOR-targeted therapeutic drugs that are developed for the treatment of pain or opiate addiction may concomitantly influence immune responses [6].
  • Here we show that all of the major behavioral effects of morphine, including locomotor activation, analgesia, tolerance, reward, and physical dependence and withdrawal symptoms, are attenuated in mice lacking adenylyl cyclase type 5 (AC5), a form of adenylyl cyclase that is highly enriched in striatum [7].
  • After ingesting street drugs sold as "PCP," "THC," and "methadone," three young men developed schizophreniform psychoses, analgesia, anesthesia, and amnesia for the psychotic state [8].
  • In addition, no changes in pain threshold were noted with alphaxalone (8 mg/kg) in the tail-flick analgesia test [9].
  • Role of sodium cromoglycate on analgesia, locomotor activity and opiate withdrawal in mice [10].

High impact information on Analgesia


Chemical compound and disease context of Analgesia

  • The alpha-adrenergic antagonist phentolamine and the catecholaminergic selective neurotoxin 6-hydroxydopamine, used to block tonic catecholamine activity in endogenous opioid-mediated analgesia systems, prevented the hyperalgesia induced by intrathecal PGE2 [15].
  • Plasma concentrations, maximum regional brain concentrations, and specific regional binding in the brain after administration of 0, 0.1, and 0.2 mg/kg doses of (S)-ketamine were measured in a randomized, double-blind, crossover study in five volunteers and were related to induced effects such as analgesia, amnesia, and mood changes [16].
  • In contrast, ligated animals treated with saline or lidocaine at 0.15 or 0.33mg/kg/h exhibited hyperalgesia on Day 3 after surgery, indicating that these lower doses of lidocaine failed to provide analgesia [17].
  • Correlations between plasma pethidine concentration, analgesia and side effects such as respiratory depression, have been established, but considerable overlap exists between concentrations producing therapeutic and non-therapeutic effects [18].
  • These observations support the theory that subanesthetic doses of i.v. ketamine (0.5 mg/kg bolus followed by 0.25 mg/kg per h) given during anesthesia reduce wound hyperalgesia and are a useful adjuvant in perioperative balanced analgesia [19].

Biological context of Analgesia


Anatomical context of Analgesia


Associations of Analgesia with chemical compounds

  • Altered nociception, analgesia and aggression in mice lacking the receptor for substance P [1].
  • Previous work has established a role for adenosine in a diverse array of neural phenomena, which include regulation of sleep and the level of arousal, neuroprotection, regulation of seizure susceptibility, locomotor effects, analgesia, mediation of the effects of ethanol, and chronic drug use [29].
  • The fentanyl significantly reduced the sensory intensity without reducing the unpleasantness of the tooth pulp stimuli, indicating that the mechanisms of narcotic analgesia may include a significant attenuation in pain sensation in addition to effects on pain reaction [30].
  • Inescapable foot shock in rats caused profound analgesia that was antagonized by naloxone or dexamethasone when shock was delivered intermittently for 30 minutes, but not when it was delivered continuously for 3 minutes [31].
  • Nitrous oxide produced a dose-related "analgesia" in mice (median effective dose, 55 percent) [32].

Gene context of Analgesia

  • Lowering Pgp expression significantly enhanced systemic morphine analgesia and prevented tolerance, but diminished the analgesic activity of centrally administered morphine, implying that supraspinal analgesia resulted from a combination of central and peripheral mechanisms activated by morphine transported from the brain to the blood [33].
  • We found that women with two variant MC1R alleles displayed significantly greater analgesia from the kappa-opioid, pentazocine, than all other groups [34].
  • To assess the relative roles of the two enzymes in pain processing, we compared responses of COX-1- or COX-2-deficient homozygous and heterozygous mice with wild-type controls in the hot plate and stretching tests for analgesia [35].
  • Intracerebroventricular injection of NPB produces analgesia to s.c. formalin injection in rats [36].
  • The analysis of responses of mutant mice to exogenous opiates has definitely clarified the essential role of MOR in both morphine analgesia and addiction, and demonstrated that DOR and KOR remain promising targets for pain treatment [37].

Analytical, diagnostic and therapeutic context of Analgesia


  1. Altered nociception, analgesia and aggression in mice lacking the receptor for substance P. De Felipe, C., Herrero, J.F., O'Brien, J.A., Palmer, J.A., Doyle, C.A., Smith, A.J., Laird, J.M., Belmonte, C., Cervero, F., Hunt, S.P. Nature (1998) [Pubmed]
  2. Alterations in nociception and body temperature after intracisternal administration of neurotensin, beta-endorphin, other endogenous peptides, and morphine. Nemeroff, C.B., Osbahr, A.J., Manberg, P.J., Ervin, G.N., Prange, A.J. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  3. Trigeminal and dorsal root ganglion neurons express CCK receptor binding sites in the rat, rabbit, and monkey: possible site of opiate-CCK analgesic interactions. Ghilardi, J.R., Allen, C.J., Vigna, S.R., McVey, D.C., Mantyh, P.W. J. Neurosci. (1992) [Pubmed]
  4. Treatment of osteoarthritis with aspartame. Edmundson, A.B., Manion, C.V. Clin. Pharmacol. Ther. (1998) [Pubmed]
  5. Paracetamol with and without codeine in acute pain: a quantitative systematic review. Moore, A., Collins, S., Carroll, D., McQuay, H. Pain (1997) [Pubmed]
  6. Abolition of morphine-immunosuppression in mice lacking the mu-opioid receptor gene. Gavériaux-Ruff, C., Matthes, H.W., Peluso, J., Kieffer, B.L. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  7. Adenylyl cyclase type 5 (AC5) is an essential mediator of morphine action. Kim, K.S., Lee, K.W., Lee, K.W., Im, J.Y., Yoo, J.Y., Kim, S.W., Lee, J.K., Nestler, E.J., Han, P.L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Prolonged psychosis attributed to phencyclidine: report of three cases. Rainey, J.M., Crowder, M.K. The American journal of psychiatry. (1975) [Pubmed]
  9. Anxiolytic activity of steroid anesthetic alphaxalone. Britton, K.T., Page, M., Baldwin, H., Koob, G.F. J. Pharmacol. Exp. Ther. (1991) [Pubmed]
  10. Role of sodium cromoglycate on analgesia, locomotor activity and opiate withdrawal in mice. Leza, J.C., Lizasoain, I., Martín-Clark, O.S., Lorenzo, P. Psychopharmacology (Berl.) (1992) [Pubmed]
  11. Stress-induced analgesia: adaptive pain suppression. Amit, Z., Galina, Z.H. Physiol. Rev. (1986) [Pubmed]
  12. Interaction with vesicle luminal protachykinin regulates surface expression of delta-opioid receptors and opioid analgesia. Guan, J.S., Xu, Z.Z., Gao, H., He, S.Q., Ma, G.Q., Sun, T., Wang, L.H., Zhang, Z.N., Lena, I., Kitchen, I., Elde, R., Zimmer, A., He, C., Pei, G., Bao, L., Zhang, X. Cell (2005) [Pubmed]
  13. Effects of caffeine on analgesia from transcutaneous electrical nerve stimulation. Marchand, S., Li, J., Charest, J. N. Engl. J. Med. (1995) [Pubmed]
  14. Desensitization of G protein-coupled receptors and neuronal functions. Gainetdinov, R.R., Premont, R.T., Bohn, L.M., Lefkowitz, R.J., Caron, M.G. Annu. Rev. Neurosci. (2004) [Pubmed]
  15. Prostaglandins inhibit endogenous pain control mechanisms by blocking transmission at spinal noradrenergic synapses. Taiwo, Y.O., Levine, J.D. J. Neurosci. (1988) [Pubmed]
  16. Central nervous system effects of subdissociative doses of (S)-ketamine are related to plasma and brain concentrations measured with positron emission tomography in healthy volunteers. Hartvig, P., Valtysson, J., Lindner, K.J., Kristensen, J., Karlsten, R., Gustafsson, L.L., Persson, J., Svensson, J.O., Oye, I., Antoni, G. Clin. Pharmacol. Ther. (1995) [Pubmed]
  17. Continual systemic infusion of lidocaine provides analgesia in an animal model of neuropathic pain. Smith, L.J., Shih, A., Miletic, G., Miletic, V. Pain (2002) [Pubmed]
  18. Clinical pharmacokinetics of pethidine. Mather, L.E., Meffin, P.J. Clinical pharmacokinetics. (1978) [Pubmed]
  19. 'Balanced analgesia' in the perioperative period: is there a place for ketamine? De Kock, M., Lavand'homme, P., Waterloos, H. Pain (2001) [Pubmed]
  20. Morphine mimics the cardioprotective effect of ischemic preconditioning via a glibenclamide-sensitive mechanism in the rat heart. Schultz, J.E., Hsu, A.K., Gross, G.J. Circ. Res. (1996) [Pubmed]
  21. The alpha2a adrenergic receptor subtype mediates spinal analgesia evoked by alpha2 agonists and is necessary for spinal adrenergic-opioid synergy. Stone, L.S., MacMillan, L.B., Kitto, K.F., Limbird, L.E., Wilcox, G.L. J. Neurosci. (1997) [Pubmed]
  22. Pharmacokinetics, efficacy, and safety of analgesia with a focus on tramadol HCl. Gibson, T.P. Am. J. Med. (1996) [Pubmed]
  23. Metkephamid and meperidine analgesia after episiotomy. Bloomfield, S.S., Barden, T.P., Mitchell, J. Clin. Pharmacol. Ther. (1983) [Pubmed]
  24. Intrathecal capsaicin depletes substance P in the rat spinal cord and produces prolonged thermal analgesia. Yaksh, T.L., Farb, D.H., Leeman, S.E., Jessell, T.M. Science (1979) [Pubmed]
  25. Randomised comparison of combined spinal-epidural and standard epidural analgesia in labour. Collis, R.E., Davies, D.W., Aveling, W. Lancet (1995) [Pubmed]
  26. Efficacy of lignocaine analgesia during treatment to the cervix. Rogstad, K.E., White, D.J., Ahmed-Jushuf, I.H. Lancet (1992) [Pubmed]
  27. Heterologous desensitization of opioid receptors by chemokines inhibits chemotaxis and enhances the perception of pain. Szabo, I., Chen, X.H., Xin, L., Adler, M.W., Howard, O.M., Oppenheim, J.J., Rogers, T.J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  28. Neurophysiological and biochemical changes evoked by valproic acid in the central nervous system. Cotariu, D., Zaidman, J.L., Evans, S. Prog. Neurobiol. (1990) [Pubmed]
  29. The role and regulation of adenosine in the central nervous system. Dunwiddie, T.V., Masino, S.A. Annu. Rev. Neurosci. (2001) [Pubmed]
  30. Narcotic analgesia: fentanyl reduces the intensity but not the unpleasantness of painful tooth pulp sensations. Gracely, R.H., Dubner, R., McGrath, P.A. Science (1979) [Pubmed]
  31. Opioid and nonopioid mechanisms of stress analgesia. Lewis, J.W., Cannon, J.T., Liebeskind, J.C. Science (1980) [Pubmed]
  32. Nitrous oxide "analgesia": resemblance to opiate action. Berkowitz, B.A., Ngai, S.H., Finck, A.D. Science (1976) [Pubmed]
  33. Transport of opioids from the brain to the periphery by P-glycoprotein: peripheral actions of central drugs. King, M., Su, W., Chang, A., Zuckerman, A., Pasternak, G.W. Nat. Neurosci. (2001) [Pubmed]
  34. The melanocortin-1 receptor gene mediates female-specific mechanisms of analgesia in mice and humans. Mogil, J.S., Wilson, S.G., Chesler, E.J., Rankin, A.L., Nemmani, K.V., Lariviere, W.R., Groce, M.K., Wallace, M.R., Kaplan, L., Staud, R., Ness, T.J., Glover, T.L., Stankova, M., Mayorov, A., Hruby, V.J., Grisel, J.E., Fillingim, R.B. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  35. Nociception in cyclooxygenase isozyme-deficient mice. Ballou, L.R., Botting, R.M., Goorha, S., Zhang, J., Vane, J.R. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  36. Characterization of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8. Tanaka, H., Yoshida, T., Miyamoto, N., Motoike, T., Kurosu, H., Shibata, K., Yamanaka, A., Williams, S.C., Richardson, J.A., Tsujino, N., Garry, M.G., Lerner, M.R., King, D.S., O'Dowd, B.F., Sakurai, T., Yanagisawa, M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  37. Exploring the opioid system by gene knockout. Kieffer, B.L., Gavériaux-Ruff, C. Prog. Neurobiol. (2002) [Pubmed]
  38. Morphine analgesia potentiated but tolerance not affected by active immunization against cholecystokinin. Faris, P.L., McLaughlin, C.L., Baile, C.A., Olney, J.W., Komisaruk, B.R. Science (1984) [Pubmed]
  39. Effect of epidural vs parenteral opioid analgesia on the progress of labor: a meta-analysis. Halpern, S.H., Leighton, B.L., Ohlsson, A., Barrett, J.F., Rice, A. JAMA (1998) [Pubmed]
  40. Pain modulation by release of the endogenous cannabinoid anandamide. Walker, J.M., Huang, S.M., Strangman, N.M., Tsou, K., Sañudo-Peña, M.C. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  41. Clinical experience with oral methadone administration in the treatment of pain in 196 advanced cancer patients. De Conno, F., Groff, L., Brunelli, C., Zecca, E., Ventafridda, V., Ripamonti, C. J. Clin. Oncol. (1996) [Pubmed]
  42. The peptidergic organization of the cat periaqueductal gray. II. The distribution of immunoreactive substance P and vasoactive intestinal polypeptide. Moss, M.S., Basbaum, A.I. J. Neurosci. (1983) [Pubmed]
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