Recent basic science research has greatly added to our knowledge of pain mechanisms. Application of this knowledge to cancer pain syndromes has led to new and innovative approaches to cancer pain management.
Methods
The mechanisms involved in the three main cancer pain syndromes (somatic, visceral, and neuropathic) are reviewed, and various therapeutic options are discussed.
Results
Advances in knowledge in neurophysiology, neuroanatomy, and pharmacology have allowed a greater understanding of the peripheral and central mechanisms of pain. New drugs and interventional techniques based on this knowledge have improved the control of cancer pain.
Conclusions
Understanding the neurophysiology of cancer pain promotes use of the most appropriate palliative measures for pain control.
PortenoyR.K.Cancer pain: pathophysiology and syndromes. Lancet.1992; 339: 1026–1031.
3.
FoleyK.M.The treatment of cancer pain. N Engl J Med.1985; 313: 84–95.
4.
WillisW.D.The Pain System: the Neural Basis of Nociceptive Transmission in the Mammalian Nervous System.Basel, Switzerland: Karger; 1985.
5.
FitzgeraldM., LynnB.The sensitization of high threshold mechanoreceptors with myelinated axons by repeated heating. J Physiol.1977; 265: 549–563.
6.
CarltonS.M., CoggeshallR.E.Nociceptive integration: does it have a peripheral component?Pain Forum.1998; 7: 71–78.
7.
CarpenterK.J., DickensonA.H.NMDA receptors and pain: hopes for novel analgesics. Reg Anesth Pain Med.1999; 24: 506–508.
8.
DickensonA.H.Spinal cord pharmacology of pain. Br J Anaesth.1995; 75: 193–200.
9.
WoolfC.J., ChongM.S.Preemptive analgesia: treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg.1993; 77: 362–379.
10.
WillisW.D., WestlundK.N.Neuroanatomy of the pain system and of the pathways that modulate pain. J Clin Neurophysiol.1997; 14: 2–31.
11.
SandoukP., SerrieA., UrtizbereaM.Morphine pharmacokinetics and pain assessment after intracerebroventricular administration in patients with terminal cancer. Clin Pharmacol Ther.1991; 49: 442–448.
12.
LenziA., GallaiG., GandolfiniM.Intraventricular morphine in paraneoplastic painful syndrome of the cervicofacial region: experience in thirty-eight cases. Neurosurgery.1985; 17: 6–11.
13.
JensenT.S.Opioids in the brain: supraspinal mechanisms in pain control. Acta Anaesthesiol Scand.1997; 41: 123–132.
14.
FieldsH.L., BasbaumA.Central nervous system mechanisms of pain modulation. In: WallP.D., MelzackR., eds. Textbook of Pain.Edinburgh, Scotland: Churchill Livingstone; 1994.
15.
KhanZ.P., FergusonC.N., JonesR.M.Alpha-2 and imidazoline receptor agonists: their pharmacology and therapeutic role. Anaesthesia.1999; 54: 146–165.
16.
HoweJ.R., WanJ-Y, YakshT.L.Selective antagonism of the antinociceptive effect of intrathecally applied alpha adrenergic agonists by intrathecal prazosin and intrathecal yohimbine. J Pharmacol Exp Ther.1983; 224: 552–558.
17.
KuraishiY., HirotaN., SatoY.Noradrenergic inhibition of the release of substance P from primary afferents in the rabbit spinal dorsal horn. Brain Res.1985; 359: 177–182.
18.
KlimschaW., TongC., EisenachJ.C.Intrathecal alpha-2-adrenergic agonists stimulate acetylcholine and norepinephrine release from the spinal cord dorsal horn in sheep: an in vivo microdialysis study. Anesthesiology.1997; 87: 110–116.
19.
LeeY-W, YakshT.L.Analysis of drug interaction between intrathecal clonidine and MK-801 in peripheral neuropathic pain rat model. Anesthesiology.1995; 82: 741–748.
20.
EisenachJ.C., DuPenS., DuboisN.Epidural clonidine analgesia for intractable cancer pain: the Epidural Clonidine Study Group. Pain.1995; 61: 391–399.
21.
StamfordJ.A.Descending control of pain. Br J Anaesth.1995; 75: 217–227.
22.
BjurholmA., KreicbergsA., BrodinE.Substance P- and CGRP: immunoreactive nerves in bone. Peptides.1988; 9: 165–171.
23.
CampaJAIII, PayneR.The management of intractable bone pain: a clinician's perspective. Semin Nucl Med.1992; 22: 3–10.
24.
FoleyK.M.Pain assessment and cancer pain syndromes. In: DoyleD., HanksG.W., Mc DonaldN., eds. Oxford Textbook of Palliative Medicine.Oxford Medical Publications: Oxford, England; 1993: 148–165.
25.
AdamiS.Bisphosphonates in prostate carcinoma. Cancer.1997; 80: 1674–1679.
26.
KanisJ.A., McCloskeyE.V.Bone turnover and biochemical markers in malignancy. Cancer.1997; 80: 1538–1545.
27.
TaubeT., BenetonM.N.C., McCloskeyE.V.Abnormal bone remodelling in patients with myelomatosis and normal biochemical indices of bone resorption. Eur J Haematol.1992; 49: 192–198.
28.
OhyaK., YamadaS., FelixR.Effect of bisphosphonates on prostaglandin synthesis by rat bone cells and mouse calvaria in culture. Clin Sci.1985; 69: 403–411.
29.
FulfaroF., CasuccioA., TicozziC.The role of bisphosphonates in the treatment of painful metastatic bone disease: a review of phase III trials. Pain.1998; 78: 157–169.
30.
NeedhamP.R., HoskinP.J.Radiotherapy for painful bone metastases. Palliat Med.1994; 8: 95–104.
31.
GilbertH.A., KaganA.R., NussbaumH.Evaluation of radiation therapy for bone metastases: pain relief and quality of life. AJR Am J Roentgenol.1977; 129: 1095–1096.
32.
HoskinP.Using radioisotopes for bone metastases. Eur J Palliative Care.1994; 11: 78–82.
CerveroF.Sensory innervation of the viscera: peripheral basis of visceral pain. Physiol Rev.1994; 74: 95–138.
35.
CerveroF.Visceral nociceptors. In: BelmonteC., CerveroF., eds. Neurobiology of Nociceptors.Oxford, England: Oxford University Press; 1996: 220–240.
36.
CerveroF., JanigW.Visceral nociceptors: a new world order?Trends Neurosci.1992; 15: 374–378.
37.
HablerH-J, JanigW., KoltzenbergM.Activation of unmyelinated afferent fibers by mechanical stimuli and inflammation of the urinary bladder in the cat. J Physiol (Lond).1990; 425: 545–562.
38.
McMahonS.B., KoltzenbergM.Silent afferents and visceral pain. In: Pharmacological Approaches to the Treatment of Chronic Pain: New Concepts and Critical Issues. Progress in Pain Research and Management. Vol 1. Seattle, Washington: IASP Press; 1994: 11–30.
39.
NessT.J., GebhartG.F.Visceral pain: a review of experimental studies. Pain.1990; 41: 167–234.
40.
GoligherJ.C., HughesE.S.R.Sensibility of the rectum and colon: its role in the mechanism of anal continence. Lancet.1951; 1–2: 543–548.
41.
GiamberardinoM.A., VecchietL.Pathophysiology of visceral pain. Curr Rev Pain.1996; 1: 23–33.
42.
CerveroF.Pathophysiology of referred pain and hyperalgesia from viscera. In: VecchietL., Albe-fessardD., LindblomU., eds. New Trends in Referred Pain and Hyperalgesia, Pain Research and Clinical Management. Vol 7. Amsterdam: Elsevier Science; 1993: 35–46.
43.
GiamberardinoM.A., VecchietL.Experimental studies on pelvic pain. Pain Rev.1994; 1: 104–117.
44.
Al-ChaerE.D., LawandN.B., WestlundK.N.Pelvic visceral input into the nucleus gracilis is largely mediated by the postsynaptic dorsal column pathway. J Neurophysiol.1996; 76: 2675–2690.
45.
Al-ChaerE.D., LawandN.D., WestlundK.N.Visceral nociceptive input into the ventral posterolateral nucleus of thalamus: a new function for the dorsal column pathway. J Neurophysiol.1996; 76: 2661–2674.
46.
Al-ChaerE.D., FengY., WillisW.D.A role for the dorsal column in nociceptive visceral input into the thalamus of primates. J Neurophysiol.1998; 79: 3143–3150.
47.
FengY., CuiM., Al-ChaerE.D.Epigastric antinociception by cervical dorsal column lesions in rats. Anesthesiology.1998; 89: 411–420.
48.
GildenbergP.L., HirshbergR.M.Limited myelotomy for the treatment of intractable cancer pain. J Neurol Neurosurg Psychiatry.1984; 47: 94–96.
49.
HirshbergR.M., Al-ChaerE.D., LawandN.B.Is there a pathway in the posterior funiculus that signals visceral pain?Pain.1996; 67: 291–305.
50.
NautaH.J.W., HewittE., WestlundK.N.Surgical interruption of a midline dorsal column visceral pain pathway: case report and review of the literature. J Neurosurg.1997; 86: 538–542.
51.
Van DongenR.T.M., CrulB.J.P., De BockM.Long-term intrathecal infusion of morphine and morphine/bupivacaine mixtures in the treatment of cancer pain: a retrospective analysis of 51 cases. Pain.1993; 55: 119–123.
52.
IschiaS., IschiaA., PolatiE.Three posterior percutaneous celiac plexus block techniques: a prospective randomized study in 61 patients with pancreatic cancer pain. Anesthesiology.1992; 76: 534–540.
53.
de Leon-CasasolaO.A.Neurolytic blocks of the sympathetic axis for the treatment of visceral pain in cancer. Curr Rev Pain.1999; 3: 173–177.
54.
OchoaJ., TorebjorkH.E., CulpW.J.Abnormal spontaneous activity in single sensory nerve fibers in humans. Muscle Nerve.1982; 5: S74–S77.
55.
DevorM.The pathophysiology of damaged peripheral nerves. In: WallP.D., MelzackR., eds. Textbook of Pain.Edinburgh, Scotland: Churchill Livingstone; 1994: 79–100.
McQuayH.Opioids in pain management. Lancet.1999; 353: 2229–2232.
59.
BesseD., LombardM.C., ZakacJ.M.Pre- and postsynaptic distribution of mu, delta and kappa opioid receptors in the superficial layers of the cervical dorsal horn of the rat spinal cord. Brain Res.1990; 521: 15–22.
60.
XuX.J., PukeM.J.C., VergeV.M.K.Up-regulation of cholecystokinin in primary sensory neurons is associated with morphine insensitivity in experimental neuropathic pain in the rat. Neurosci Lett.1993; 152: 129–132.
61.
StanfaL.C., SullivanA.F., DickensonA.H.Alterations in neuronal excitability and the potency of spinal mu, delta and kappa opioids after carrageenan induced inflammation. Pain.1992; 50: 345–354.
62.
SuzukiR., ChapmanV., DickensonA.H.The effectiveness of spinal and systemic morphine on rat dorsal horn neuronal responses in the spinal nerve ligation model of neuropathic pain. Pain.1999; 80: 215–228.
63.
NovakovicS.D., TzoumakaE., McGivernJ.G.Distribution of the tetrodotoxin-resistant sodium channel PN3 in rat sensory neurons in normal and neuropathic conditions. J Neurosci.1998; 18: 2174–2187.
64.
KingeryW.S.A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes. Pain.1997; 73: 123–139.
65.
RowbothamM., HardenN., StaceyB.Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA.1998; 280: 1837–1842.
66.
BackonjaM., BeydounA., EdwardsK.R.Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial. JAMA.1998; 280: 1831–1836.
67.
JaveryK.B., UsseryT.W., StegerH.G.Comparison of morphine and morphine with ketamine for postoperative analgesia. Can J Anaesth.1996; 43: 212–215.
68.
MercadanteS.Ketamine in cancer pain: an update. Palliat Med.1996; 10225–10230.
69.
PudD., EisenbergE., SpitzerA.The NMDA receptor antagonist amantadine reduces surgical neuropathic pain in cancer patients: a double-blind, randomised, placebo-controlled trial. Pain.1998; 75: 349–354.
