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Pain Therapeutics - Drugs, Markets and Companies

  • ID: 39076
  • Report
  • March 2017
  • Region: Global
  • 579 Pages
  • Jain PharmaBiotech
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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 173 of these are profiled in the report along with 151 collaborations. These are a mix of pharmaceutical companies and biotechnology companies.

The worldwide analgesic markets were analyzed for the year 2016 and projected to 2026. 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 72 tables, 22 figures, and 600 selected references to the literature.

Note: Product cover images may vary from those shown
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0. Executive Summary

1. Basic Aspects of Pain
Historical aspects of pain
Pain definitions
A glossary of terms relevant to pain
Pain classification and description
Neuropathic pain
Refractory neuropathic pain
Classification of neuropathic pain according to levels
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
Modulation of pain by pictures associated with social contacts
Modulation of pain by emotions
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
Chemokines as mediators of neuropathic pain
Chemotherapy-induced neuropathic pain
CNS innate immunity and neuropathic pain
Cytokines as mediators of neuropathic pain
Free radicals in generation of neuropathic pain
GABA deficiency in neuropathic pain
Genetic basis of neuropathic pain
Gene expression changes in neuropathic pain
Glial activation and neuropathic pain
Immune cell-derived opioids and neuropathic pain
Spinal leptin and neuropathic pain
Tetrahydrobiopterin regulates neuropathic pain sensitivity
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
Acid-sensing ion channels
Calcium channels in pain
P2X3 ion channels
Potassium ion channels
Sodium ion channels in pain
TRP ion channels in pain
Genetic basis of pain
Alternative RNA splicing and pain
Study of genes in pain
Pain as a channelopathy
Pain in the brain
Effect of chronic pain on opioid receptors in the brain
Neuropathic pain-induced morphological changes in the brain
Change from acute to chronic pain
Acute versus chronic pain
Descending facilitatory modulation of pain
Development of chronic pain following severe accidental injury
Pain and transcriptional repressor DREAM
Role of neuronal plasticity in pain
Role of epigenetics in development of chronic pain
Concluding remarks on evolution of acute pain into chronic pain
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
Substance P
Excitatory amino acids
Role of nitric oxide in pain
Protein kinase C
Adenosine and adenosine receptors
Vitamin D and pain
Vanilloid receptor
TRPA and TRPV 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
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
NeuroDigm GEL Model™ of neuropathic 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
Quality of pain intensity assessment in clinical research studies
Quantitative sensory testing
Pain measurement tools for neonates and children
Quantitative sensory testing
Microneurographic recordings
Psychological assessment of pain
Testing for in vivo pain processing
Brain imaging in pain
fMRI for study of pain
PET for study of pain
PET correlated with fMRI and evoked potentials
Patient outcomes and quality of life during treatment for chronic pain
Collection and analysis of data on pain patients
Evaluation of analgesics in humans
Early phase clinical trials of analgesics in humans
Design of clinical trials for pain
Assessment of neuropathic pain
Transdermal electrical stimulation for study of chronic 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
Mechanism of action of currently used pain medications
Non-steroidal antiinflammatory drugs
COX-2 inhibitors
Side effects of COX inhibitors
Innovative COX-2 inhibitors in development
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
N-methyl-D-aspartate receptor antagonists
CNS 5161
Triptans for treatment of non-migrainous pain
Local anesthetics
Topical application
Nerve blocks
Injection of local anesthetics for analgesia
Ultrasound-guided nerve blocks
Topical salicylates for the treatment of pain
Topical rubefacients for acute and chronic pain in adults
Adjunctive analgesics
Mechanism of analgesic action of antidepressants
Antiepileptic drugs
Mechanism of action of antiepileptic drugs in neuropathic pain
Valproic acid
Other antiepileptic drugs
Botulinum toxins
Analgesic effect of botulinum toxin A
Engineered botulinum toxin
Analgesics from traditional medical systems
Herbs and other plants
Analgesics derived from cobra toxin

4. Management of Pain
Sites for pain management
Self-medication at home
Physicians' offices
Major hospitals
Pain centers
Non-pharmacological approaches to pain
Alternative medicine
Self-Controlled Energo Neuro Adaptive Regulation
Behavioral therapy
Cognition and pain
Control over brain activation and pain by using functional MRI
Mindfulness meditation for relief of chronic pain
Thermal-grill illusion
Virtual reality therapy
Local application of heat
Transcutaneous nerve stimulation
Non-invasive brain stimulation techniques for chronic pain.
Transcranial magnetic stimulation
Cranial electrotherapy 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
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 for acute pain
Reasons for inadequate management of acute pain
Perioperative pain management
Devices for delivery of analgesics in the postoperative period
Drug combination for perioperative pain
Gabapentin for reduction of postoperative pain
Ketamine for perioperative pain
Opioids for perioperative pain
Perioperative pain in neurosurgery
Prolonged duration local anesthesia
Concluding remarks on the management of postoperative pain
Pain in the intensive care unit
Pain associated with sports and exercise
Pain associated with trauma
Chronic abdominal pain
Functional somatic syndromes
Fibromyalgia syndrome
Pathomechanism of FMS
Management of FMS
New developments in pharmacotherapy of FMS
Irritable bowel syndrome
Opioids for IBS
Tricyclic antidepressants for IBS
Serotonin-modulating drugs for IBS
Musculoskeletal pain
Myofascial pain syndrome
Pathomechanism of osteoarthritis
Pain aggravates osteoarthritis by crosstalk between CNS and the joint
Management of 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 and sciatica
Lumbar disc disease and sciatica
Management of back pain with analgesics
Miscellaneous medical therapies for backache and sciatica
Neck pain
Chronic pelvic pain
Cancer pain
Adjuvant drugs for cancer pain
Alternative non-pharmacological methods
Anesthetic techniques
Management of bone pain in cancer
Non-opioid analgesics for cancer pain
Opioid treatment of cancer pain
Opioid breakthrough pains
Opioid-induced enhancement of cancer growth and its prevention
Opioids delivery methods for cancer pain
Opioid administration through implanted drug delivery devices
Radiation therapy
Surgical methods of cancer pain relief
Conclusions regarding management of cancer pain
Chronic non-malignant pain
Cluster headache
Chronic daily headache
Indomethacin-responsive headache
Occipital neuralgia
Paroxysmal hemicrania
Tension headache
Management of acute migraine
Neurostimulation for migraine
Transcranial magnetic stimulation for migraine
Transnasal sphenopalatine ganglion block by catheter
Migraine prophylaxis
Pediatric migraine
Trigeminal neuralgia
Dental pain
Neuropathic pain
Pathogenesis of neuropathic pain
Chronobiology of neuropathic pain as guide to therapy
Management of neuropathic pain based on mechanism
Guidelines for the management of neuropathic pain
Pharmacotherapy of neuropathic pain
Evidence-based management of neuropathic pain
Management of central neuropathic pain
Neurosurgical approaches to central neuropathic pain
Management of neuropathic pain in syringomyelia
Neuropathic pain associated with spinal cord injury
Peripheral neuropathic pain
Truncal neuropathic pain
Management of postsurgical peripheral neuropathic pain
Management of chemotherapy-induced pain
Morton’s neuroma
Management of peripheral diabetic neuropathy
Postherpetic neuralgia
Complex regional pain syndrome
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
Ophthalmic pain
Pain in Parkinson's disease
Pain in sickle cell disease
Management of chronic unexplained pain
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
Misuse of codeine in children
Management of pain in the elderly
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 cognitively impaired elderly people
Management of pain in brain-damaged minimally conscious patients
Management of pain in the terminally ill
Problems in the management of pain
Inadequate pain management
Problems with use of opioids
Regulation of use of opioids
Guideline for use of opioids
Suggestions for improvement of pain management by healthcare providers
Management of neuropathic pain refractory to first line treatment
Multidisciplinary approaches to pain management
Pain as the fifth vital sign
Reassessment of management of chronic pain

5. Drug Delivery for Pain
Intra-articular injection for relief of joint pain
Delivery of analgesics to peripheral nerves
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
Glide SDI® solid dose injector
SUMAVEL™ DosePro™ needle-less injection
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
Transdermal trans-capsaicin
Powder Injection Systems
Intranasal delivery of analgesics
Intranasal morphine
Intranasal morphine derivatives
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
Intrathecal delivery of analgesics
Anatomical & physiological aspects of intrathecal drug delivery
Pharmacokinetics of intrathecal drug delivery
Epidural drugs
Pharmacokinetics of analgesic drugs following epidural injection
Epidural glucocorticoids
Epidural etanercept
Epidural morphine
Intrathecal drugs
Intrathecal adenosine
Intrathecal baclofen
Intrathecal fadolmidine
Intrathecal lidocaine
Intrathecal magnesium sulfate
Intrathecal midazolam
Intrathecal opioids
Intrathecal neostigmine
Intrathecal octeoride
Intrathecal non-NMDA antagonists
Intrathecal prostaglandin antagonists
Intrathecal resiniferatoxin
Intrathecal ziconotide
Combinations of intrathecal agents for relief of pain
Pumps for intrathecal delivery of analgesics
Complications of intrathecal delivery of analgesics
Concluding remarks on intrathecal delivery of analgesic agents
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
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
Activation of P2X7 receptors
Alfa2-adrenergic receptor agonists
Angiotensin II type 2 receptor
Anti-NGF strategies
Bradykinin antagonists
Cannabinoid receptor agonists
Capsaicin and VR1 receptor-based analgesics
Vanilloid (capsaicin) receptor antagonists
VR1 receptor agonists
CCR2 receptor blockade
Cholecystokinin antagonists
Cholinergic receptor agonists
Conotoxins as analgesics
Corticotropin-releasing factor
FAAH inhibitors
FKBP51 as a target for treatment of chronic pain
Free radical scavengers as analgesics
Superoxide dismutase mimetics
GABA analogues
Subtype-selective GABAergic drugs
Glutamate receptor antagonists
NMDA receptor modulation for neuropathic pain
Alternatives to direct blocking of NMDA receptors
Glycine antagonists
Metabotropic glutamate receptors
Histogranin-like compounds for the management of pain
Ion channels as targets for analgesic drugs
Acid-sensing ion channels as drug target
Calcium channel blockers
HCN1 channels as targets for propofol analogs for neuropathic pain
P2X ion channel receptor antagonists
Sodium channel modulation
Mas-related GPCR agonists
Microsomal prostaglandin E synthase inhibitors
NAALADase inhibitors
Neuropeptide receptor antagonists for improving the efficacy of opioids
Neurotrophic factor-based pain therapeutics
Glial cell line-derived neurotrophic factor
Nerve growth factor antagonists
Newer COX inhibitors
COX-3 inhibitors
Dual cyclooxygenase/lipoxygenase inhibitors
Nicotinic acetylcholine receptors
Mode of action of nACh/neural nicotinic receptor agonists
Potential of central nACh/neural nicotinic 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
Norepinephrine transporter inhibition
Opioid peptide receptors ligands
Opioids with unique receptor characteristics
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
Somatostatin analogs
Substance P and neurokinin receptor antagonists
Substance P-Saporin
Targeting prostanoid synthesis
Tetrodotoxin based analgesics
TRPV1 modulators
TRPV1 antagonists
TRPV1 agonists
TRPV1-mediated entry of sodium channel blocker QX-314
TRPV1 receptors regulate longevity
Tumor necrosis factor-? antagonists
Biological therapies for pain
Cell therapy for pain
Cells for delivery of antinociceptive molecules
Cell therapy for low back pain
Cell therapy for knee pain due to degenerative disorders
Cell therapy for peripheral neuropathic pain
Cell transplantation for relief of pain
Transplantation of chromaffin cells
Transplantation of stem cells
Transplantation of astrocytes secreting enkephalin
Transplantation of cells for relief of neuropathic pain
Concluding remarks on cell therapy for pain
Gene therapy for pain
Rationale of gene therapy for pain
Gene therapy of peripheral neuropathy
Gene therapy targeted to neuroimmune component of chronic pain
Methods of gene delivery for pain
Vectors for gene therapy of pain
Vectors for endogenous analgesic production in cranial neuralgias
Methods of gene delivery for pain
Gene delivery by intrathecal route
Gene transfer to the dorsal nerve roots
Gene transfer by injections into the brain substance
Antisense therapy for pain
RNAi-based approaches for pain therapy
Potential applications of gene therapy for management of pain
Gene therapy for producing enkephalin to block pain signals
Gene therapy for upregulation of BMP in backache
Gene therapy for targeting nuclear factor-?B
Gene therapy for neuropathic pain
Zinc finger DNA-binding protein therapeutic for chronic pain
Concluding remarks about gene therapy for pain
Preclinical development of pain drugs
NGF-blocking antibody
Prostatic acid phosphatase as a novel analgesic
Preclinical development of drugs for neuropathic pain
5-HT receptor agonists
a9a10 antagonists
Central nACh receptor agonists
CGP 35024
Drugs that suppress glial activation
NCX 8001
Targeting tumor necrosis factor
Future targets for osteoarthritic pain
Pain drugs in clinical trials
Clinical trials of miscellaneous drugs for pain
Drugs in clinical trials for postsurgical pain
Cox-2 inhibitors in clinical trials
Clinical trials of disease modifying therapies for arthritis
Drugs in clinical development for neuropathic pain
Adenosine A1 agonists for neuropathic pain
Ajulemic acid
AVP-923 (dextromethorphan + quinidine)
Botulinum toxin type A
D-amino acid oxidase inhibitors
V3381 (indantadol)
Drug discovery and development for migraine
Drugs in clinical development for migraine
Clinical development of preventive therapies for migraine
Drug development for visceral pain

7. Safety, Regulatory and Legal issues of pain management
Safety issues of analgesics
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
Addiction and development of tolerance
Chronic pain and opioid addiction
Companies developing products to deter abuse of opioids
Hyperalgesia associated with opioids
Narcotic bowel syndrome
Opioid use disorder
Opioid withdrawal
Opioid-associated constipation
Respiratory depression
Adverse effects of use of opioids in non-malignant pain
Pharmacogenetics of adverse effects of codeine
PEGylated naloxol
Innovative approaches to modify opioid pharmacology
Adverse effects of miscellaneous non-narcotic analgesics
Adverse effects of immunosuppressants used for relief of pain
Adverse effects of acetaminophen
Hyponatremia as an adverse effect of tramadol
Regulatory issues
DEA and use of opioids for pain relief in terminal care
FDA and COX-2 inhibitors
Legal issues of COX-2 inhibitors
Regulatory aspects of opioid safety and abuse
Opioid misuse and regulatory agencies
FDA measures for safety of opioid use
Misuse of fentanyl
Regulation of extended release and long-acting opioids
Pain relief as a legal right
Pain relief and the WHO

8. Pain Markets
Epidemiological basis of pain markets
Neuropathic pain
Trigeminal neuralgia
Multiple sclerosis
Irritable bowel syndrome
Chronic pelvic pain
Chronic pain due to traumatic brain injury
Postsurgical pain
Economics of pain
Pain as a driver of healthcare costs
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
Fibromyalgia market
Pain markets based on drugs
Nonsteroidal antiinflammatory drugs
Transdermal pain therapeutics
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
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 management of pain
Genetic factors in response to pain
Genetic mutations with loss of pain
Genetic mutations and painful conditions
Mechanism-specific management of pain
Pharmacogenomics and pharmacogenetics of pain
Personalized management of pain with commonly used analgesics
Pharmacogenomics and pharmacogenetics of opioids
Pharmacogenetics of NSAIDs
Preoperative testing to tailor postoperative analgesic requirements
Role of conditioned pain modulation in personalized management of pain
Signature of pain on brain imaging
Strategies for improving pain management
Research on pain in Europe

10. Companies Involved in Pain Therapeutics
Profiles of companies

11. References

List of Tables
Table 1-1: Landmarks in the history of pain therapeutics
Table 1-2: Classification of 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:Monoclonal antibodies as disease modifying therapies in rheumatoid arthritis
Table 4-5: Causes of chronic backache
Table 4-6: Management of chronic pelvic pain
Table 4-7: Management of pain in cancer
Table 4-8: Definitions of tolerance, physiological dependence, withdrawal and addiction
Table 4-9: A simplified classification of headache
Table 4-10: Various methods for the management of migraine
Table 4-11: Management of neuropathic pain based on mechanism and diagnosis
Table 4-12: Management of central neuropathic pain
Table 4-13: Current management of peripheral diabetic neuropathy
Table 4-14: Treatment strategies for postherpetic neuralgia
Table 4-15: Management of complex regional pain syndrome
Table 4-16: Methods of treating phantom limb pain
Table 4-17: Treatment of chronic unexplained pain due to central sensitization
Table 4-18: Anti-itching therapies
Table 4-19: Suggested improvements in the management of pain
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: Approved drugs for spinal administration for pain
Table 5-4: Off-label intrathecal use of drugs for for pain
Table 5-5: Experimental studies of intrathecal administration of drugs for analgesia
Table 5-6: Intrathecal drugs for pain in clinical trials
Table 5-7: Comparison of pharmacokinetics of lipophilic with hydrophilic opioids
Table 5-8: Delivery systems for pain (other than intrathecal) in clinical development
Table 6-1: Classification of drugs in development for pain
Table 6-2: Preclinical studies on cannabinoid (CB2) receptor agonists as analgesics
Table 6-3: Cannabinoid receptor agonists in clinical development as analgesics
Table 6-4: NO-related therapies for pain
Table 6-5: Major opioids receptors and their ligands
Table 6-6: Strategies to counteract pain at various levels at periphery and in the CNS
Table 6-7: Types of TRPV1 antagonists
Table 6-8: TRPV1 antagonists in clinical trials
Table 6-9: Biological therapies for pain
Table 6-10: Experimental gene therapy approaches for relief of pain
Table 6-11: Selected preclinical approaches to pain therapy
Table 6-12: Selected preclinical drugs for neuropathic pain
Table 6-13: Selected clinical trials of miscellaneous drugs for pain
Table 6-14: Selected clinical trials of drugs for postsurgical pain
Table 6-15: COX-2 inhibitors in clinical development
Table 6-16: Disease modifying drugs for arthritis in clinical trials
Table 6-17: Clinical trials of drugs for neuropathic pain
Table 6-18: Selected drugs in clinical development for migraine
Table 6-19: Therapeutic targets for treating visceral pain
Table 7-1: Companies with products to deter abuse of opioids
Table 7-2: Diagnostic criteria for an opioid-use disorder
Table 8-1: Market values for various painful conditions 2016-2026
Table 8-2: Changes in market shares of drugs for neuropathic pain 2016-2026
Table 8-3: Markets for pain according to therapies 2016-2026
Table 8-4: Distribution of value of pain therapeutics in major markets 2016-2026
Table 8-5: Distribution of value of opioids in major pain markets 2016-2026
Table 8-6: Distribution of value of NSAIDs in major pain markets 2016-2026
Table 8-7: Strategies for developing pain markets
Table 9-1: P450 isoforms in the metabolism of drugs used in the management of pain
Table 10-1: Top companies in pain therapeutics
Table 10-2: Product pipeline of Adolor Corporation
Table 10-3: Selected collaborations in the area of pain management

List of 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 3-1: Pathway of metabolism of codein
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 5-1: Powder Injection Systems
Figure 5-2: Penetration of CSF into spinal cord
Figure 5-3: Disposition of opioids after intrathecal administration
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: Essential components of personalized management of pain
Figure 9-3: Genetic and non-genetic factors affecting efficacy and side effects of opioids

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Professor K. K. Jain is a neurologist/neurosurgeon by training and has been working in the biotechnology/biopharmaceuticals industry for several years. He received graduate training in both Europe and USA, has held academic positions in several countries and is a Fellow of the Faculty of Pharmaceutical Medicine of the Royal Colleges of UK. Currently he is a consultant at Jain PharmaBiotech. Prof. Jain is the author of 415 publications including 16 books (2 as editor) and 48 special reports, which have covered important areas in biotechnology, gene therapy and biopharmaceuticals.
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