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Pain Therapeutics

Drugs, Markets and Companies

Publication Date   March 2008
Publisher   Jain PharmaBiotech
Product Type   Strategic Report
Pages   469
ISBN Number   not applicable
Product Code   JAI018
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Summary


This report describes the latest concepts of pathomechanisms of pain as a basis for management and development of new pharmacotherapies for pain. Major segments of the pain market are arthritis, neuropathic pain and cancer pain. Because pain is a subjective sensation, it is difficult to evaluate objectively in clinical trials. Various tools for pain measurement are described, including brain imaging.

Most of the currently used analgesic drugs fall into the categories of opioids and nonsteroidal antiinflammatory drugs such as COX-2 inhibitors. Non-opioid analgesics include ketamine, a N-methyl-D-aspartate receptor antagonist. Adjuvant analgesics include antidepressants and antiepileptic drugs used for the treatment of neuropathic pain. Management of pain is multidisciplinary and includes both pharmacological and non-pharmacological methods such as acupuncture, transcutaneous electrical nerve stimulation and surgery. Various pain syndromes require different approaches in management, for example, the main category of drugs for migraine are triptans such as sumatriptan.

Drug delivery is an important consideration in pain treatment. Controlled release preparations provide a steady delivery of analgesics. Well-known non-injection methods such astransdermal, pulmonary and intranasal application have been used. Topical analgesics and local anesthetics are also available. Devices such as implanted pumps are used for delivery of drugs such as opioids intrathecally (introduction into spinal subarachnoid space by lumbar puncture) in patients with cancer pain.

The wide variety of drugs in development includes opioid receptor ligands, bradykinin antagonists, mPGES-1 inhibitors, glutamate receptor antagonists, substance P and neurokinin receptor antagonists, norepinephrine transporter inhibitors,P2X2 neuron receptor antagonists and nitric oxide-based analgesics. A number of cannabinoids are also in development for pain. Fish-derived tetrodotoxin was initially focused on indication of opiate addiction withdrawal but is found to have an analgesic action as well. Cone shells contain therapeutically useful peptides including the conotoxins, and one such peptide, ziconotide, has been approved. Various cell and gene therapies are also being developed for the management of pain.

Advances in molecular and biological techniques are markedly advancing our undestanding of pain. Understanding the pathophysiology of pain is an important factor in discovery of rational therapies for pain. Advances in pharmacogenomics and pharmacogenetics are enabling the development of personalized approaches to the management of pain.

Over 500 companies have been identified to be involved in developing or marketing pain therapeutics and 145 of these are profiled in the report along with 138 collaborations. These are a mix of pharmaceutical companies and biotechnology companies.

The worldwide analgesic markets were analyzed for the year 2007 and projected to 2017. Calculations are based on the epidemiology of various painful conditions and the development of analgesic drugs and devices. Unfulfilled needs for analgesics are identified and strategies are outlined to develop markets for analgesic drugs.The report is supplemented with 60 tables, 19 figures, and 500 selected references to the literature.

Content


  • 0. Executive Summary
  • 1. Basic Aspects of Pain
    • Introduction
    • Historical aspects of pain
    • Pain definitions
    • A glossary of terms relevant to pain
    • Pain classification and description
    • Neuropathic pain
    • Cancer pain
    • Bone pain in cancer
    • Complex regional pain syndrome
    • Mechanisms of pain
    • Pain pathways
    • Role of nociceptors in pain transmission
    • Gate control and neuromatrix theories of pain
    • Pain mediators
    • Role of the sympathetic nervous system in pain
    • Visceral pain
    • Pathomechanism of visceral pain
    • Pathomechanism of neuropathic pain
    • Role of intact nerve fibers in neuropathic pain
    • Role of cytokines
    • Role of chemokines
    • Glial activation and neuropathic pain
    • Role of CNS innate immunity
    • Genetic basis of neuropathic pain
    • Gene expression changes in neuropathic pain
    • Role of free radicals in generation of neuropathic pain
    • Chemotherapy-induced neuropathic pain
    • Regulation of pain sensitivity by tetrahydrobiopterin
    • Pathomechanism of migraine
    • Role of the immune system in pain
    • Pain and itch
    • Pathomechanism of itch
    • Clinical aspects of itch
    • Molecular pathophysiology of pain
    • Role of ion channels in pain
    • Role of sodium channels in pain
    • Role of potassium ion channels
    • Role of calcium channels in pain
    • Acid-sensing ion channels
    • P2X3 ion channels
    • Role of TRP ion channels in pain
    • Genetic basis of pain
    • Study of genes in pain
    • Pain in the brain
    • Change from acute to chronic pain
    • Role of neuronal plasticity in pain
    • Descending facilitatory modulation of pain
    • Pain and transcriptional repressor DREAM
    • Neurochemistry of pain
    • Molecular elements of pain in the peripheral nervous system
    • Molecular elements of pain in the central nervous system
    • Opioid receptors
    • Role of AMPA receptors in chronic pain
    • Kinins
    • Serotonin
    • Substance P
    • Excitatory amino acids
    • Role of nitric oxide in pain
    • Prostaglandins
    • Endocannabinoids
    • Protein kinase C
    • Adenosine and adenosine receptors
    • Vitamin D and pain
    • Vanilloid receptor
    • TRPA1 and TRPV1 receptors
    • Endothelin-B receptors
    • Nerve growth factor and pain
    • Adrenomedullin as a pain-related peptide
    • Biomarkers of pain
    • Biomarkers of visceral pain
  • 2. Assessment of Pain and Analgesics
    • Introduction
    • Animal models of pain
    • An overview
    • Selection of animal species as models for pain
    • Types of noxious stimuli
    • Animal models of neuropathic pain
    • Animal models of arthritis
    • Animal models of peripheral neuropathy
    • Limitations of current pain models
    • Biogenic Animal Model of Chronic Pain
    • Ethical issues concerning animal pain models
    • Medical evaluation of pain
    • Chronic pain as a manifestation of various diseases
    • Assessment of pain patients
    • Medical examination
    • Measurement of pain
    • Quantitative sensory testing
    • Pain measurement tools for neonates and children
    • Quantitative sensory testing
    • Psychological assessment of pain
    • Brain imaging in pain
    • Patient outcomes and quality of life during treatment for chronic pain
    • Evaluation of analgesics
    • Study of pain in humans
    • Testing of analgesics in humans
    • Design of clinical trials for pain
    • Assessment of neuropathic pain
    • Placebo effect in pain
    • Role of electronic pain recording in determination of the placebo effect
    • Outcome measures for chronic pain trials
    • Pain, pain therapies and cognitive function
  • 3. Pharmacotherapy of Pain
    • Introduction
    • Mechanism of action of currently used pain medications
    • Non-steroidal antiinflammatory drugs
    • COX-2 inhibitors
    • Celecoxib
    • Nimesulide
    • Rofecoxib
    • Valdecoxib
    • Lumiracoxib
    • Side effects of COX inhibitors
    • Safety aspects of COX-2 inhibitors in development
    • Acetaminophen
    • Antioxidants as analgesics
    • Opiates and opioids
    • Innovations in opioid therapy
    • Oral transmucosal fentanyl
    • Use of opioids for chronic non-cancer pain
    • Opioid receptor modulation for visceral pain
    • Opiorphin
    • N-methyl-D-aspartate receptor antagonists
    • Ketamine
    • CNS 5161
    • Triptans for treatment of non-migrainous pain
    • Capsaicin
    • NGX-4010
    • Local anesthetics
    • Topical application
    • Nerve blocks
    • Injection of local anesthetics for analgesia
    • Topical salicylates for the treatment of pain
    • Adjunctive analgesics
    • Antidepressants
    • Mechanism of analgesic action of antidepressants
    • Antiepileptic drugs
    • Mechanism of action of antiepileptic drugs in neuropathic pain
    • Carbamazepine
    • Gabapentin
    • Lamotrigine
    • Phenytoin
    • Pregabalin
    • Topiramate
    • Valproic acid
    • Other antiepileptic drugs
    • Clonidine
    • Baclofen
    • Corticosteroids
    • Calcitonin
    • Bisphosphonates
    • Botulinum toxins
    • Analgesic effect of botulinum toxin A
    • Engineered botulinum toxin
    • Adverse effects of analgesics
    • Gastrointestinal adverse effects of NSAIDs
    • Measures to reduce gastrointestinal adverse effects of NSAIDs
    • Cardiovascular adverse effects of COX-2 inhibitors
    • Adverse effects of opioids
    • Risk of addiction and development of tolerance
    • Hyperalgesia associated with opioids
    • Respiratory depression
    • Opioid-associated constipation
    • Approaches to reduce adverse effects of opioids
    • PEGylated naloxol
    • Remoxy versus Oxycontin
    • Innovative approaches to modify opioid pharmacology
    • Adverse effects of non-narcotic analgesics
  • 4. Management of Pain
    • Introduction
    • Sites for pain management
    • Self-medication at home
    • Physicians' offices
    • Major hospitals
    • Pain centers
    • Non-pharmacological approaches to pain
    • Alternative medicine
    • Acupuncture
    • Herbs and other plants
    • Aromatherapy
    • Self-Controlled Energo Neuro Adaptive Regulation
    • Behavioral therapy
    • Cognition and pain
    • Control over brain activation and pain by using functional MRI
    • Virtual reality therapy
    • Local application of heat
    • Transcutaneous nerve stimulation
    • Transcranial magnetic stimulation
    • Neurosurgery for pain relief
    • Ablative procedures on the nervous system
    • Procedures on peripheral, spinal and cranial nerves
    • Vagal nerve stimulation for control of pain
    • Neuromodulation
    • Spinal cord stimulation
    • Brain stimulation
    • Implantation of drug delivery devices
    • Management of special types of pain
    • Acute pain
    • Management of acute renal colic: NSAIDS vs. opioids
    • Combination of opioids and NSAIDs
    • Reasons for inadequate management of acute pain
    • Perioperative pain management
    • Opioids for perioperative pain
    • Ketamine for perioperative pain
    • Drug combination for perioperative pain
    • Perioperative pain in neurosurgery
    • Devices for delivery of analgesics in the postoperative period
    • Pain associated with sports and exercise
    • Chronic abdominal pain
    • Functional somatic syndromes
    • Fibromyalgia syndrome
    • Pathomechanism of FMS
    • Management of FMS
    • New developments in pharmacotherapy of FMS
    • Erythromelalgia
    • Irritable bowel syndrome
    • Opioids for IBS
    • Tricyclic antidepressants for IBS
    • Serotonin-modulating drugs for IBS
    • Musculoskeletal pain
    • Myofascial pain syndrome
    • Osteoarthritis
    • Rheumatoid arthritis
    • Management of pain in rheumatoid arthritis
    • Disease modifying therapies in rheumatoid arthritis
    • Resurgence of interest in gold-based treatments for RA
    • Backache
    • Use of analgesics for management of back pain
    • Miscellaneous medical therapies for backache and sciatica
    • Neck pain
    • Chronic pelvic pain
    • Prostatitis
    • Cancer pain
    • Opioid treatment of cancer pain
    • Breakthrough and opioid-insensitive pains
    • Methods of delivery of opioids for cancer pain
    • Implantation of drug delivery devices
    • Management of bone pain in cancer
    • Use of non-opioid analgesics for cancer pain
    • Adjuvant drugs for cancer pain
    • Radiation therapy
    • Alternative non-pharmacological methods
    • Anesthetic techniques
    • Surgical methods of cancer pain relief
    • Conclusions regarding management of cancer pain
    • Chronic non-malignant pain
    • Headache
    • Migraine
    • Management of acute migraine
    • Neurostimulation for migraine
    • Transcranial magnetic stimulation for migraine
    • Cluster headache
    • Tension headache
    • Chronic daily headache
    • Trigeminal neuralgia
    • Dental pain
    • Neuropathic pain
    • Management of central neuropathic pain
    • Pharmacotherapy of central neuropathic pain
    • Chronobiology of neuropathic pain as guide to therapy
    • Neurosurgical approaches to central neuropathic pain
    • Syringomyelia
    • Neuropathic pain associated with spinal cord injury
    • Peripheral neuropathic pain
    • Management of chemotherapy-induced pain
    • Morton's neuroma
    • Management of diabetic neuropathy
    • Postherpetic neuralgia
    • Complex regional pain syndrome
    • Evidence-based management of neuropathic pain
    • An algorithm for the management of peripheral neuropathic pain
    • Phantom limb pain
    • Pathomechanism of phantom limb pain
    • Management of phantom limb pain
    • Pain and depression
    • Neurochemical link between pain and depression
    • Management of chronic pain and depression
    • Miscellaneous painful conditions
    • Burning mouth syndrome
    • Chronic unstable angina
    • Mastalgia
    • Ophthalmic pain
    • Pain in Parkinson's disease
    • Management of itching
    • Topical applications for itching
    • Systemic therapies for itching
    • Non-pharmacological therapies for itch
    • Management of pain in special population groups
    • Racial and ethnic differences in pain management
    • Pain in neonates
    • Management of pain in children
    • Management of pain in the elderly
    • Management of pain in the cognitively impaired elderly people
    • Management of pain in women
    • Reasons for increased pain perception in women
    • Chronic pelvic pain in women
    • Gender differences in response to analgesics
    • Considerations for pain management in women
    • Management of pain in neurologically handicapped persons
    • Management of pain in the terminally ill
    • Deficiencies in the management of pain
    • Negative physician attitudes in pain management
    • Suggestions for improvement of pain management by healthcare providers
    • Pain as the fifth vital sign
    • Multidisciplinary approaches to pain management
    • Pharmacoeconomic aspects of pain management
  • 5. Drug Delivery for Pain
    • Introduction
    • Intra-articular injection for relief of joint pain
    • Controlled release drug delivery for pain
    • Accelerating the effect of subcutaneous morphine
    • Controlled drug delivery at site of pain
    • Oral extended release opioids
    • Extended release oral morphine
    • Controlled release oxycodone
    • Extended release oxymorphone
    • Oral extended release tramadol
    • Extended release gabapentin
    • Use of nanotechnology for drug delivery for pain
    • Non-injection methods of delivery of analgesics
    • Topical applications for pain
    • Topical local anesthetics
    • Topical NSAIDs
    • Topical and transdermal diclofenac
    • Topical application for postoperative pain
    • Needle-free drug delivery for pain
    • Transdermal drug delivery for pain
    • Relief of pain associated with minor medical procedures
    • Transdermal fentanyl
    • Transdermal ketoprofen
    • Transdermal nitroglycerine as an adjuvant to opioids
    • Transdermal buprenorphine
    • Powder Injection Systems
    • Intranasal delivery of analgesics
    • Intranasal morphine
    • Intranasal diamorphine
    • Intranasal fentanyl
    • Intranasal buprenorphine
    • Intranasal ketamine
    • Intranasal ketorolac
    • Nasal formulations for migraine
    • Oral spray formulations for migraine
    • Delivery of analgesics by inhalation
    • Buccal transmucosal and sublingual delivery of analgesics
    • Application for cancer pain
    • Application for non-cancer pain
    • Pumps for drug delivery in pain
    • Patient controlled analgesia
    • Postoperative pain pumps
    • Chronogesic (sufentanil) Pain Therapy System
    • Spinal pumps for delivery of analgesics
    • Spinal delivery of analgesics
    • Epidural administration of encapsulated morphine
    • Epidural dexamethasone
    • Intrathecal ziconotide
    • Intrathecal CGX1160
    • Intrathecal neostigmine
    • Intrathecal prostaglandin antagonists
    • Intrathecal non-NMDA antagonists
    • Intrathecal fadolmidine
    • Intrathecal resiniferatoxin
    • Intracerebroventricular morphine for pain
    • Development of drug delivery systems for pain therapy
    • Delivery of analgesics to the CNS across the blood brain barrier
    • Drug delivery systems in clinical trials
  • 6. Drug Development for Pain
    • Introduction
    • Drugs in development for pain
    • Current research goals
    • The ideal analgesic
    • Pain R & D goals in the pharmaceutical industry
    • Drug targets in the spinal cord
    • Drug targets in the brain
    • Molecular targets for analgesic drugs
    • Opioid peptide receptors ligands
    • Buprenorphine
    • Nociceptin
    • Opioid analgesics acting outside the CNS
    • Opioid analgesics acting at peripheral receptors
    • Peripherally acting mu-opioid receptor agonists
    • Targeting of opioid peptide-containing immune cells
    • Advantages of peripherally selective opioid drugs
    • Neuropeptide receptor antagonists for improving the efficacy of opioids
    • Nicotinic acetylcholine receptors
    • Mode of action of nACh/neural nicotinic receptor agonists
    • Potential of central nACh/neural nicotinic receptor agonists
    • Tumor necrosis factor-? antagonists
    • Bradykinin antagonists
    • Newer COX inhibitors
    • COX-3 inhibitors
    • Dual cyclooxygenase/lipoxygenase inhibitors
    • Microsomal prostaglandin E synthase inhibitors
    • Glutamate receptor antagonists
    • NMDA receptor modulation for neuropathic pain
    • NMDA subunit antagonists
    • Glycine antagonists
    • Metabotropic glutamate receptors
    • NAALADase inhibitors
    • ?2-adrenergic receptor agonists
    • Norepinephrine transporter inhibition
    • Capsaicin and VR1 receptor-based analgesics
    • VR1 receptor agonists
    • Vanilloid (capsaicin) receptor antagonists
    • Substance P and neurokinin receptor antagonists
    • Adenosine receptor agonists
    • Ion channels as drug targets
    • Acid-sensing ion channels as drug target
    • P2X ion channel receptor antagonists
    • TRPV1-mediated entry of sodium channel blocker QX-314
    • Targeting prostanoid synthesis
    • Cholinergic receptor agonists
    • Nitric oxide-based analgesics
    • Nitric oxide-releasing NSAIDs
    • Pharmacology of NO-SAIDs
    • COX-inhibiting nitric oxide donors
    • NO-donating structures to extend life cycle of existing analgesics
    • Nitric oxide mimetics
    • Neuronal nitric oxide synthase inhibitors
    • Inhibitors of heme oxygenase
    • Free radical scavengers as analgesics
    • Superoxide dismutase mimetics
    • Ion channels as targets for analgesic drugs
    • Calcium channel blockers
    • Sodium channel modulation
    • GABA analogues
    • Subtype-selective GABAergic drugs
    • Cholecystokinin antagonists
    • CCR2 receptor blockade
    • Cannabinoids
    • Cannabinoid receptor agonists
    • Cannabidiol
    • Cannabinor
    • Nabilone
    • Somatostatin analogues
    • Corticotropin-releasing factor
    • Tetrodotoxin based analgesics
    • Conotoxins as analgesics
    • Substance P-Saporin
    • Nerve growth factor antagonists
    • Glial cell line-derived neurotrophic factor
    • Use of histogranin-like compounds for the management of pain
    • Cell and gene therapies for pain
    • Cell therapy
    • Implantation of chromaffin cells
    • Cells for delivery of antinociceptive molecules
    • Cell therapy for low back pain
    • Gene therapy
    • Gene delivery by intrathecal route
    • Gene transfer to the dorsal nerve roots
    • Gene transfer by injections into the brain substance
    • Zinc finger DNA-binding protein therapeutic for chronic pain
    • Gene therapy for producing enkephalin to block pain signals
    • Antisense therapy for pain
    • siRNA for relief of neuropathic pain
    • Preclinical development of pain drugs
    • NGF-blocking antibody
    • Preclinical development of drugs for neuropathic pain
    • 5-HT receptor agonists
    • AM1241
    • Artemin/Neuroblastin
    • Capsazepine
    • Central nACh receptor agonists
    • Drugs that suppress glial activation
    • Erythropoietin
    • Targeting tumor necrosis factor
    • CGP 35024
    • NCX 8001
    • NR2B subtype NMDA receptor ligands
    • NW-1029
    • R116301
    • Zonisamide
    • Future targets for osteoarthritic pain
    • Pain drugs in clinical trials
    • Clinical trials of miscellaneous drugs for pain
    • Alvimopan
    • Asimadoline
    • EN3202
    • Oxytrex
    • Drugs in clinical trials for postsurgical pain
    • Bicifadine
    • DepoMorphine
    • TC-2696
    • Cox-2 inhibitors in clinical trials
    • Monoclonal antibodies for pain relief
    • Clinical trials of disease modifying therapies for rheumatoid arthritis
    • Drugs in clinical development for neuropathic pain
    • Adenosine A1 agonists for neuropathic pain
    • CPL7075
    • Glyx-13
    • IP-751
    • Lacosamide
    • Oxcarbazepine
    • Ralfinamide
    • Retigabine
    • SB-509
    • SCP-1
    • TC-6499
    • Tebanicline
    • Tezampanel
    • Thalidomide
    • TRO19622
    • V3381
    • XP-13512
    • Drugs in development for migraine
    • Drug development for visceral pain
  • 7. Legal and regulatory issues of pain management
    • Pain relief as a legal right
    • Pain relief and the WHO
    • Regulatory issues
    • Opioids and cannabinoids
    • DEA and use of opioids for pain relief in terminal care
    • FDA and COX-2 inhibitors
    • Legal issues of COX-2 inhibitors
    • Misuse of analgesics
    • Opioids and regulatory agencies
    • Misuse of fentanyl
  • 8. Pain Markets
    • Introduction
    • Epidemiological basis of pain markets
    • Cancer
    • Neuropathic pain
    • Trigeminal neuralgia
    • Arthritis
    • Backache
    • Migraine
    • Multiple sclerosis
    • Irritable bowel syndrome
    • Chronic pelvic pain
    • Postsurgical pain
    • Disability and financial loss through pain
    • Pain markets based on painful conditions
    • The cancer pain market
    • The arthritis pain market
    • Postsurgical pain market
    • The backache market
    • The headache market
    • Neuropathic pain market
    • Pain markets based on drugs
    • Opioids
    • Nonsteroidal antiinflammatory drugs
    • Anesthesia
    • Antiepileptic drugs as analgesics
    • Other drugs
    • Hospital vs retail share of pain market
    • Hospital versus retail opioid market
    • Devices for pain
    • Pain markets according to geographical areas
    • Cost effectiveness of various approaches
    • Unfulfilled R&D needs in pain therapy
    • Under treatment of pain
    • Unfulfilled needs in drug development for chronic pain
    • Strategies for developing pain markets
    • Finding alternatives to intrathecal administration for chronic pain
    • Development of other applications of analgesic drugs
    • Partnership of patients, pharmacists and companies
    • Factors that may influence future pain markets
    • Drivers of pain markets
    • Public surveys as indicators of impact of pain on people
    • Effect of regulatory reviews on markets for pain products
    • Novel versus older therapies for pain
  • 9. Future of Pain Therapeutics
    • Introduction
    • Advances in the understanding of pain
    • Pathogenesis of chronic pain
    • Role of glia in neuropathic pain
    • Molecular and neurobiological techniques
    • Improved understanding of cancer pain
    • Advances in drug discovery and development for pain
    • Novel targets for drug discovery for pain
    • PTH2 receptor
    • Modulators of endogenous cannabinoids
    • Application of new technologies to pain therapeutics
    • Application of nanobiotechnology to pain therapeutics
    • Technologies for the manufacture of analgesics
    • Future trends and needs in pain management
    • Pain management in future healthcare systems
    • Systems biology approach to pain
    • Personalized pain management
    • Pharmacogenomics and pharmacogenetics of pain
    • Mechanism-specific management of pain
    • Preoperative testing to tailor postoperative analgesic requirements
    • Strategies for improving pain management
  • 10. Companies Involved in Pain Therapeutics
    • Introduction
    • Profiles of companies
    • Collaborations
  • 11. References
  • Tables
    • Table 1 1: Landmarks in the history of pain therapeutics
    • Table 1 2: Classification of chronic pain
    • Table 1 3: Classification of neuropathic pain
    • Table 1 4: Classification of chronic cancer pain according to cause
    • Table 1 5: Percentage of patients with pain according to the type of cancer
    • Table 1 6: Key molecular elements of pain in the peripheral nervous system
    • Table 1 7: Key molecular elements of pain in the central nervous system
    • Table 2 1: IASP guidelines for the use of animals in pain studies
    • Table 2 2: Chronic pain as a manifestation of other diseases
    • Table 2 3: Recommendations for assessing patient satisfaction with pain management
    • Table 3 1: Classification of some currently used pain medications according to mechanism
    • Table 3 2: Drugs used for the treatment of pain
    • Table 3 3: Selective COX-2 inhibitors in clinical use for pain
    • Table 3 4: Antiepileptic drugs with analgesic effect
    • Table 4 1: Non-pharmacological approaches to management of pain
    • Table 4 2: Companies involved in neuromodulation therapy for pain
    • Table 4 3: Reasons for the inadequate management of acute pain
    • Table 4 4: Causes of chronic backache
    • Table 4 5: Management of chronic pelvic pain
    • Table 4 6: Management of pain in cancer
    • Table 4 7: Definitions of tolerance, physiological dependence, withdrawal and addiction
    • Table 4 8: A simplified classification of headache
    • Table 4 9: Various methods for the management of migraine
    • Table 4 10: Management of central neuropathic pain
    • Table 4 11: Management of neuropathic pain based on mechanism and diagnosis
    • Table 4 12: Current management of painful diabetic neuropathy
    • Table 4 13: Treatment strategies for postherpetic neuralgia
    • Table 4 14: Management of complex regional pain syndrome
    • Table 4 15: Methods of treating phantom limb pain
    • Table 4 16: Anti-itching therapies
    • Table 5 1: A classification of drug delivery methods used in management of pain
    • Table 5 2: Selected marketed non-injection drug delivery systems for pain
    • Table 5 3: Spinal administration of drugs for pain
    • Table 5 4: Selected drug delivery systems for pain in clinical development
    • Table 6 1: Classification of drugs in development for pain
    • Table 6 2: Major opioids receptors and their ligands
    • Table 6 3: Strategies to counteract pain at various levels at periphery and in the CNS
    • Table 6 4: NO-related therapies for pain
    • Table 6 5: Cannabinoid receptor agonists in clinical development as analgesics
    • Table 6 6: Preclinical studies on cannabinoid (CB2) receptor agonists as analgesics
    • Table 6 7: Experimental gene therapy approaches for relief of pain
    • Table 6 8: Selected preclinical approaches to pain therapy
    • Table 6 9: Selected preclinical drugs for neuropathic pain
    • Table 6 10: Selected clinical trials of miscellaneous drugs for pain
    • Table 6 11: Selected clinical trials of drugs for postsurgical pain
    • Table 6 12: Novel COX-2 inhibitors in clinical development
    • Table 6 13: Disease modifying antirheumatic drugs in clinical trials
    • Table 6 14: Clinical trials of drugs for neuropathic pain
    • Table 6 15: Selected drugs in development for migraine
    • Table 6 16: Therapeutic targets for treating visceral pain
    • Table 8 1: Market values for various painful conditions 2007-2017
    • Table 8 2: Markets for pain according to therapies 2007-2017
    • Table 8 3: Distribution of value of pain therapeutics in major markets 2007-2017
    • Table 8 4: Distribution of value of opioids in major pain markets 2007-2017
    • Table 8 5: Distribution of value of NSAIDs in major pain markets 2007-2017
    • Table 8 6: Strategies for developing pain markets
    • Table 9 1: P450 isoforms in the metabolism of drugs used in the management of pain
    • Table 10 1: Product pipeline of Adolor Corporation
    • Table 10 2: Endo Pharmaceuticals' products in clinical trials
    • Table 10 3: Selected collaborations in the area of pain management
  • Figures
    • Figure 1 1: Afferent pain pathways
    • Figure 1 2: Evolution of the gate control theory
    • Figure 1 3: The body self-neurometric
    • Figure 1 4: Various ligands and receptors on the peripheral terminals of nociceptive nerve fibers
    • Figure 1 5: Prostaglandin biosynthesis pathway
    • Figure 2 1: Biopsychosocial factors that interact and modulate the experience of pain
    • Figure 2 2: Pain intensity scales
    • Figure 4 1: The WHO step ladder for pain
    • Figure 4 2: An algorithm for the acute management of migraine
    • Figure 4 3: Neuroimmune activation events leading to sensitization of CNS
    • Figure 4 4: An algorithm for the management of peripheral neuropathic pain
    • Figure 4 5: Algorithm for management of patients with chronic pain and depression
    • Figure 4 6: Suggested improvements in the management of pain
    • Figure 5 1: Powder Injection Systems
    • Figure 6 1: Attributes of the ideal analgesic
    • Figure 6 2: Nerve targeting drug delivery system for gene therapy of pain
    • Figure 8 1: Unfulfilled needs in the treatment for chronic pain
    • Figure 9 1: Impact of new technologies on pain therapeutics
    • Figure 9 2: A scheme of personalized management of pain"