Reportlinker Adds Pain Therapeutics - Drugs, Markets and Companies
NEW YORK, Dec. 21, 2010 /PRNewswire/ -- Reportlinker.com announces that a new market research report is available in its catalogue:
Pain Therapeutics - Drugs, Markets and Companies
http://www.reportlinker.com/p0203548/Pain-Therapeutics---Drugs-Markets-and-Companies.html
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 understanding 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 161 of these are profiled in the report along with 149 collaborations. These are a mix of pharmaceutical companies and biotechnology companies.
The worldwide analgesic markets were analyzed for the year 2009 and projected to 2019. 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 65 tables, 18 figures, and 500 selected references to the literature.
Table of Contents
0. Executive Summary 19
1. Basic Aspects of Pain 21
Introduction 21
Historical aspects of pain 21
Pain definitions 23
A glossary of terms relevant to pain 24
Pain classification and description 24
Neuropathic pain 25
Cancer pain 27
Bone pain in cancer 29
Complex regional pain syndrome 29
Mechanisms of pain 30
Pain pathways 30
Role of nociceptors in pain transmission 31
Gate control and neuromatrix theories of pain 32
Pain mediators 33
Modulation of pain by pictures associated with social contacts 33
Modulation of pain by emotions 33
Role of the sympathetic nervous system in pain 34
Visceral pain 34
Pathomechanism of visceral pain 34
Pathomechanism of neuropathic pain 35
Role of intact nerve fibers in neuropathic pain 35
Chemokines as mediators of neuropathic pain 35
Chemotherapy-induced neuropathic pain 36
CNS innate immunity and neuropathic pain 36
Cytokines as mediators of neuropathic pain 36
Free radicals in generation of neuropathic pain 36
Genetic basis of neuropathic pain 37
Gene expression changes in neuropathic pain 37
Glial activation and neuropathic pain 38
Immune cell-derived opioids and neuropathic pain 38
Spinal leptin and neuropathic pain 38
Tetrahydrobiopterin regulates neuropathic pain sensitivity 39
Pathomechanism of migraine 39
Role of the immune system in pain 40
Pain and itch 40
Pathomechanism of itch 40
Clinical aspects of itch 41
Molecular pathophysiology of pain 41
Role of ion channels in pain 41
Role of sodium channels in pain 42
Role of potassium ion channels 43
Role of calcium channels in pain 43
Acid-sensing ion channels 44
P2X3 ion channels 44
Role of TRP ion channels in pain 45
Genetic basis of pain 45
Study of genes in pain 46
Pain in the brain 47
Neuropathic pain-induced morphological changes in the brain 47
Change from acute to chronic pain 47
Descending facilitatory modulation of pain 48
Development of chronic pain following severe accidental injury 48
Pain and transcriptional repressor DREAM 49
Role of neuronal plasticity in pain 49
Neurochemistry of pain 49
Molecular elements of pain in the peripheral nervous system 49
Molecular elements of pain in the central nervous system 50
Opioid receptors 51
Role of AMPA receptors in chronic pain 51
Kinins 51
Serotonin 52
Substance P 52
Excitatory amino acids 52
Role of nitric oxide in pain 52
Prostaglandins 53
Endocannabinoids 54
Protein kinase C 54
Adenosine and adenosine receptors 55
Vitamin D and pain 55
Vanilloid receptor 55
TRPA1 and TRPV1 receptors 55
Endothelin-B receptors 57
Nerve growth factor and pain 57
Adrenomedullin as a pain-related peptide 57
Biomarkers of pain 57
Biomarkers of visceral pain 58
2. Assessment of Pain and Analgesics 59
Introduction 59
Animal models of pain 59
An overview 59
Selection of animal species as models for pain 59
Types of noxious stimuli 60
Animal models of neuropathic pain 60
Animal models of arthritis 60
Animal models of peripheral neuropathy 61
Limitations of current pain models 61
Biogenic animal model of chronic pain 62
Ethical issues concerning animal pain models 62
Medical evaluation of pain 63
Chronic pain as a manifestation of various diseases 63
Assessment of pain patients 63
Medical examination 63
Measurement of pain 64
Quantitative sensory testing 65
Pain measurement tools for neonates and children 66
Quantitative sensory testing 66
Psychological assessment of pain 67
Brain imaging in pain 67
PET for study of pain 67
PET correlated with fMRI and evoked potentials 68
Patient outcomes and quality of life during treatment for chronic pain 68
Collection and analysis of data on pain patients 69
Evaluation of analgesics in humans 69
Early phase clinical trials of analgesics in humans 69
Design of clinical trials for pain 70
Assessment of neuropathic pain 71
Transdermal electrical stimulation for study of chronic pain 71
Placebo effect in pain 72
Role of electronic pain recording in determination of the placebo effect 72
Outcome measures for chronic pain trials 73
Pain, pain therapies and cognitive function 73
3. Pharmacotherapy of Pain 75
Introduction 75
Mechanism of action of currently used pain medications 75
Non-steroidal antiinflammatory drugs 76
COX-2 inhibitors 76
Celecoxib 77
Metamizole 78
Nimesulide 78
Rofecoxib 78
Valdecoxib 79
Lumiracoxib 79
Side effects of COX inhibitors 79
Innovative COX-2 inhibitors in development 81
Acetaminophen 82
Antioxidants as analgesics 82
Opiates and opioids 82
Innovations in opioid therapy 83
Oral transmucosal fentanyl 84
Use of opioids for chronic non-cancer pain 84
Opioid receptor modulation for visceral pain 84
Opiorphin 85
N-methyl-D-aspartate receptor antagonists 85
Ketamine 85
CNS 5161 85
Triptans for treatment of non-migrainous pain 86
Capsaicin 86
NGX-4010 87
Local anesthetics 87
Topical application 87
Nerve blocks 87
Injection of local anesthetics for analgesia 87
Ultrasound-guided nerve blocks 88
Topical salicylates for the treatment of pain 88
Topical rubefacients for acute and chronic pain in adults 88
Adjunctive analgesics 88
Antidepressants 89
Mechanism of analgesic action of antidepressants 90
Antiepileptic drugs 90
Mechanism of action of antiepileptic drugs in neuropathic pain 91
Carbamazepine 92
Gabapentin 92
Lamotrigine 93
Phenytoin 93
Pregabalin 93
Topiramate 94
Valproic acid 94
Other antiepileptic drugs 95
Clonidine 95
Baclofen 95
Corticosteroids 96
Calcitonin 96
Bisphosphonates 96
Botulinum toxins 97
Analgesic effect of botulinum toxin A 97
Engineered botulinum toxin 97
Analgesics from traditional medical systems 98
Herbs and other plants 98
Analgesics derived from cobra toxin 99
Adverse effects of analgesics 99
Gastrointestinal adverse effects of NSAIDs 99
Measures to reduce gastrointestinal adverse effects of NSAIDs 99
Cardiovascular adverse effects of COX-2 inhibitors 100
Adverse effects of opioids 100
Risk of addiction and development of tolerance 100
Companies developing products to deter abuse of opioids 101
Remoxy versus Oxycontin 101
Hyperalgesia associated with opioids 102
Respiratory depression 102
Opioid-associated constipation 102
Narcotic bowel syndrome 102
Approaches to reduce adverse effects of opioids 103
PEGylated naloxol 103
Innovative approaches to modify opioid pharmacology 103
Regulatory aspects of opioid abuse, overdose and death 104
Adverse effects of miscellaneous non-narcotic analgesics 104
Adverse effects of immunosuppressants used for relief of pain 105
Adverse effects of acetaminophen 105
4. Management of Pain 107
Introduction 107
Sites for pain management 107
Self-medication at home 107
Physicians' offices 107
Major hospitals 107
Pain centers 108
Non-pharmacological approaches to pain 108
Alternative medicine 108
Acupuncture 109
Aromatherapy 109
Self-Controlled Energo Neuro Adaptive Regulation 110
Behavioral therapy 110
Cognition and pain 110
Control over brain activation and pain by using functional MRI 110
Virtual reality therapy 111
Local application of heat 111
Transcutaneous nerve stimulation 111
Transcranial magnetic stimulation 112
Neurosurgery for pain relief 112
Ablative procedures on the nervous system 112
Procedures on peripheral, spinal and cranial nerves 112
Vagal nerve stimulation for control of pain 113
Neuromodulation 113
Spinal cord stimulation 114
Brain stimulation 114
Implantation of drug delivery devices 114
Management of special types of pain 115
Acute pain 115
Management of acute renal colic: NSAIDS vs. opioids 115
Combination of opioids and NSAIDs for acute pain 115
Reasons for inadequate management of acute pain 115
Perioperative pain management 116
Devices for delivery of analgesics in the postoperative period 116
Drug combination for perioperative pain 117
Gabapentin for reduction of postoperative pain 118
Ketamine for perioperative pain 118
Opioids for perioperative pain 118
Perioperative pain in neurosurgery 119
Prolonged duration local anesthesia 119
Concluding remarks on the management of postoperative pain 119
Pain in the intensive care unit 120
Pain associated with sports and exercise 120
Pain associated with trauma 121
Chronic abdominal pain 121
Functional somatic syndromes 122
Fibromyalgia syndrome 122
Pathomechanism of FMS 122
Management of FMS 123
New developments in pharmacotherapy of FMS 123
Erythromelalgia 124
Irritable bowel syndrome 125
Opioids for IBS 125
Tricyclic antidepressants for IBS 126
Serotonin-modulating drugs for IBS 126
Musculoskeletal pain 126
Myofascial pain syndrome 126
Osteoarthritis 127
Pathomechanism of osteoarthritis 127
Pain aggravates osteoarthritis by crosstalk between CNS and the joint 128
Management of osteoarthritis 128
Rheumatoid arthritis 129
Management of pain in rheumatoid arthritis 130
Disease modifying therapies in rheumatoid arthritis 130
Resurgence of interest in gold-based treatments for RA 131
Backache 131
Use of analgesics for management of back pain 132
Miscellaneous medical therapies for backache and sciatica 133
Neck pain 134
Chronic pelvic pain 134
Prostatitis 134
Cancer pain 135
Opioid treatment of cancer pain 135
Breakthrough and opioid-insensitive pains 137
Morphine-induced enhancement of cancer growth and its prevention 137
Methods of delivery of opioids for cancer pain 137
Implantation of drug delivery devices 138
Management of bone pain in cancer 138
Use of non-opioid analgesics for cancer pain 139
Adjuvant drugs for cancer pain 139
Radiation therapy 139
Alternative non-pharmacological methods 139
Anesthetic techniques 140
Surgical methods of cancer pain relief 140
Conclusions regarding management of cancer pain 140
Chronic non-malignant pain 140
Headache 141
Migraine 142
Management of acute migraine 142
Neurostimulation for migraine 146
Transcranial magnetic stimulation for migraine 146
Migraine prophylaxis 147
Cluster headache 147
Hemicrania continua 147
Tension headache 148
Chronic daily headache 148
Trigeminal neuralgia 149
Dental pain 149
Neuropathic pain 149
Pathogenesis of neuropathic pain 150
Chronobiology of neuropathic pain as guide to therapy 150
Management of neuropathic pain based on mechanism 151
Guidelines for the management of neuropathic pain 151
Pharmacotherapy of neuropathic pain 152
Evidence-based management of neuropathic pain 154
Management of central neuropathic pain 154
Neurosurgical approaches to central neuropathic pain 155
Management of neuropathic pain in syringomyelia 155
Neuropathic pain associated with spinal cord injury 155
Peripheral neuropathic pain 156
Management of postsurgical peripheral neuropathic pain 156
Management of chemotherapy-induced pain 156
Morton's neuroma 157
Management of peripheral diabetic neuropathy 157
Postherpetic neuralgia 159
Complex regional pain syndrome 161
An algorithm for the management of peripheral neuropathic pain 162
Phantom limb pain 163
Pathomechanism of phantom limb pain 163
Management of phantom limb pain 164
Pain and depression 166
Neurochemical link between pain and depression 166
Management of chronic pain and depression 167
Miscellaneous painful conditions 168
Burning mouth syndrome 168
Chronic unstable angina 168
Mastalgia 168
Ophthalmic pain 169
Pain in Parkinson's disease 169
Management of itching 169
Topical applications for itching 170
Systemic therapies for itching 171
Non-pharmacological therapies for itch 172
Management of pain in special population groups 172
Racial and ethnic differences in pain management 172
Pain in neonates 172
Management of pain in children 173
Management of pain in the elderly 173
Management of pain in women 174
Reasons for increased pain perception in women 175
Chronic pelvic pain in women 175
Gender differences in response to analgesics 175
Considerations for pain management in women 176
Management of pain in neurologically handicapped persons 176
Management of pain in the cognitively impaired elderly people 176
Management of pain in brain-damaged minimally conscious patients 177
Management of pain in the terminally ill 177
Deficiencies in the management of pain 178
Negative physician attitudes in pain management 178
Suggestions for improvement of pain management by healthcare providers 179
Pain as the fifth vital sign 180
Management of neuropathic pain in patients refractory to first line treatment 180
Multidisciplinary approaches to pain management 180
5. Drug Delivery for Pain 182
Introduction 182
Intra-articular injection for relief of joint pain 183
Controlled release drug delivery for pain 183
Accelerating the effect of subcutaneous morphine 183
Controlled drug delivery at site of pain 183
Oral extended release opioids 184
Extended release oral morphine 184
Controlled release oxycodone 185
Extended release oxymorphone 185
Oral extended release tramadol 185
Extended release gabapentin 186
Use of nanotechnology for drug delivery for pain 186
Non-injection methods of delivery of analgesics 186
Topical applications for pain 187
Topical local anesthetics 187
Topical NSAIDs 187
Topical and transdermal diclofenac 188
Topical application for postoperative pain 189
Needle-free drug delivery for pain 189
Glide SDI® solid dose injector 189
SUMAVEL™ DosePro™ needle-less injection 189
Transdermal drug delivery for pain 189
Relief of pain associated with minor medical procedures 190
Transdermal fentanyl 190
Transdermal ketoprofen 191
Transdermal nitroglycerine as an adjuvant to opioids 192
Transdermal buprenorphine 192
Transdermal trans-capsaicin 192
Powder Injection Systems 193
Intranasal delivery of analgesics 193
Intranasal morphine 194
Intranasal morphine derivatives 194
Intranasal fentanyl 195
Intranasal buprenorphine 195
Intranasal ketamine 195
Intranasal ketorolac 196
Nasal formulations for migraine 196
Oral spray formulations for migraine 196
Delivery of analgesics by inhalation 197
Buccal transmucosal and sublingual delivery of analgesics 198
Application for cancer pain 198
Application for non-cancer pain 198
Pumps for drug delivery in pain 199
Patient controlled analgesia 199
Postoperative pain pumps 199
Chronogesic (sufentanil) Pain Therapy System 200
Spinal pumps for delivery of analgesics 201
Spinal delivery of analgesics 201
Epidural administration of analgesics 202
Epidural dexamethasone 202
Epidural etanercept 203
Epidural morphine 203
Intrathecal administration of analgesics 203
Intrathecal ziconotide 203
Intrathecal CGX1160 204
Intrathecal neostigmine 204
Intrathecal prostaglandin antagonists 204
Intrathecal non-NMDA antagonists 205
Intrathecal fadolmidine 205
Intrathecal resiniferatoxin 205
Concluding remarks on intrathecal delivery of analgesic agents 205
Intracerebroventricular morphine for pain 206
Development of drug delivery systems for pain therapy 206
Delivery of analgesics to the CNS across the blood brain barrier 206
Drug delivery systems in clinical trials 207
6. Drug Development for Pain 210
Introduction 210
Drugs in development for pain 210
Current research goals 211
The ideal analgesic 211
Pain R & D goals in the pharmaceutical industry 211
Drug targets in the spinal cord 212
Drug targets in the brain 212
Molecular targets for analgesic drugs 212
Activation of P2X7 receptors 212
Adenosine receptor agonists 213
Alfa2-adrenergic receptor agonists 213
Bradykinin antagonists 213
Cannabinoids 214
Cannabinoid receptor agonists 214
Cannabidiol 216
Cannabinor 217
Nabilone 217
Capsaicin and VR1 receptor-based analgesics 218
Vanilloid (capsaicin) receptor antagonists 218
VR1 receptor agonists 218
CCR2 receptor blockade 219
Cholecystokinin antagonists 219
Cholinergic receptor agonists 219
Conotoxins as analgesics 220
Corticotropin-releasing factor 221
FAAH inhibitors 221
PF-3845 222
URB597 222
Free radical scavengers as analgesics 222
Superoxide dismutase mimetics 223
GABA analogues 223
Subtype-selective GABAergic drugs 223
Glial cell line-derived neurotrophic factor 224
Glutamate receptor antagonists 224
NMDA receptor modulation for neuropathic pain 224
Alternatives to direct blocking of NMDA receptors 224
Glycine antagonists 225
Metabotropic glutamate receptors 225
Histogranin-like compounds for the management of pain 225
Ion channels as targets for analgesic drugs 226
Acid-sensing ion channels as drug target 226
Calcium channel blockers 227
P2X ion channel receptor antagonists 227
Sodium channel modulation 228
Mas-related GPCR agonists 228
Microsomal prostaglandin E synthase inhibitors 229
NAALADase inhibitors 230
Nerve growth factor antagonists 230
Newer COX inhibitors 230
COX-3 inhibitors 230
Dual cyclooxygenase/lipoxygenase inhibitors 231
Neuropeptide receptor antagonists for improving the efficacy of opioids 231
Nicotinic acetylcholine receptors 231
Mode of action of nACh/neural nicotinic receptor agonists 232
Potential of central nACh/neural nicotinic receptor agonists 232
Nitric oxide-based analgesics 233
Nitric oxide-releasing NSAIDs 233
Pharmacology of NO-SAIDs 234
COX-inhibiting nitric oxide donors 234
NO-donating structures to extend life cycle of existing analgesics 234
Nitric oxide mimetics 235
Neuronal nitric oxide synthase inhibitors 235
Norepinephrine transporter inhibition 235
Opioid peptide receptors ligands 236
Opioids with unique receptor characteristics 237
Buprenorphine 237
Nociceptin 237
Tapentadol 237
Opioid analgesics acting outside the CNS 238
Opioid analgesics acting at peripheral receptors 238
Peripherally acting mu-opioid receptor agonists 238
Targeting of opioid peptide-containing immune cells 239
Advantages of peripherally selective opioid drugs 239
Resolvins 239
Somatostatin analogs 240
Substance P and neurokinin receptor antagonists 240
Substance P-Saporin 241
Targeting prostanoid synthesis 241
Tetrodotoxin based analgesics 242
TRPV1 antagonists 242
TRPV1 antagonists in clinical trials 243
TRPV1-mediated entry of sodium channel blocker QX-314 243
Tumor necrosis factor-a antagonists 244
Cell and gene therapies for pain 244
Cell therapy 245
Implantation of chromaffin cells 245
Role of stem cells in management of pain 246
Implantation of astrocytes secreting enkephalin 246
Cells for delivery of antinociceptive molecules 246
Implantation of genetically engineered cells 247
Cell therapy for low back pain 247
Cell therapy for knee pain due to degenerative disorders 248
Cell therapy for peripheral neuropathy 248
Concluding remarks on cell therapy for pain 248
Gene therapy 249
Rationale of gene therapy for pain 249
Vectors for gene therapy of pain 250
Methods of gene delivery for pain 250
Vectors for endogenous analgesic production in cranial neuralgias 251
Gene delivery by intrathecal route 251
Gene transfer to the dorsal nerve roots 251
Gene therapy of peripheral neuropathy 253
Gene transfer by injections into the brain substance 253
Zinc finger DNA-binding protein therapeutic for chronic pain 253
Gene therapy for producing enkephalin to block pain signals 253
Targeting nuclear factor-kB 254
Gene therapy targeted to neuroimmune component of chronic pain 255
Antisense therapy for pain 255
RNAi-based approaches for pain therapy 255
Potential applications of gene therapy for management of pain 256
Concluding remarks about gene therapy for pain 257
Preclinical development of pain drugs 258
NGF-blocking antibody 258
Prostatic acid phosphatase as a novel analgesic 259
Preclinical development of drugs for neuropathic pain 259
5-HT receptor agonists 260
A-803467 260
AM1241 260
Artemin/Neuroblastin 261
Capsazepine 261
Central nACh receptor agonists 262
CGP 35024 262
Drugs that suppress glial activation 262
Erythropoietin 263
Gene therapy for neuropathic pain 263
NCX 8001 263
NR2B subtype NMDA receptor ligands 264
NW-1029 264
R116301 265
Targeting tumor necrosis factor 265
Future targets for osteoarthritic pain 265
Pain drugs in clinical trials 265
Clinical trials of miscellaneous drugs for pain 266
Alvimopan 267
Asimadoline 268
EN3202 268
Oxytrex 268
Drugs in clinical trials for postsurgical pain 269
Bicifadine 270
DepoMorphine 270
TC-2696 271
Cox-2 inhibitors in clinical trials 271
Clinical trials of disease modifying therapies for arthritis 272
Drugs in clinical development for neuropathic pain 273
Adenosine A1 agonists for neuropathic pain 275
Botulinum toxin type A 276
CPL7075 276
D-amino acid oxidase inhibitors 277
Glyx-13 277
IP-751 277
Lacosamide 278
Oxcarbazepine 278
Perampanel 278
Ralfinamide 278
Retigabine 279
SB-509 279
SCP-1 279
TC-6499 279
Tebanicline 280
Tezampanel 280
Thalidomide 280
TRO19622 281
V3381 (indantadol) 281
XP-13512 281
Zonisamide 282
Drug discovery and development for migraine 282
Drugs in clinical development for migraine 282
Drug development for visceral pain 285
7. Legal and regulatory issues of pain management 288
Pain relief as a legal right 288
Pain relief and the WHO 288
Regulatory issues 288
Opioids and cannabinoids 288
DEA and use of opioids for pain relief in terminal care 288
FDA and COX-2 inhibitors 289
Legal issues of COX-2 inhibitors 290
Regulatory issues of opioid safety 290
Opioid misuse and regulatory agencies 290
FDA measures for safety of opioid use 290
Misuse of fentanyl 291
8. Pain Markets 292
Introduction 292
Epidemiological basis of pain markets 292
Cancer 293
Neuropathic pain 293
Trigeminal neuralgia 293
Arthritis 293
Backache 293
Migraine 294
Multiple sclerosis 294
Irritable bowel syndrome 294
Chronic pelvic pain 294
Chronic pain due to traumatic brain injury 294
Postsurgical pain 295
Economics of pain 295
Pain as a driver of healthcare costs 295
Disability and financial loss through pain 296
Pain markets based on painful conditions 296
The cancer pain market 296
The arthritis pain market 297
Postsurgical pain market 297
The backache market 297
The headache market 298
Neuropathic pain market 298
Fibromyalgia market 299
Pain markets based on drugs 299
Opioids 299
Nonsteroidal antiinflammatory drugs 299
Transdermal pain therapeutics 300
Anesthesia 300
Antiepileptic drugs as analgesics 300
Other drugs 301
Hospital vs retail share of pain market 301
Hospital versus retail opioid market 301
Devices for pain 301
Pain markets according to geographical areas 301
Cost effectiveness of various approaches 302
Unfulfilled R&D needs in pain therapy 302
Under treatment of pain 302
Unfulfilled needs in drug development for chronic pain 303
Strategies for developing pain markets 303
Finding alternatives to intrathecal administration for chronic pain 304
Development of other applications of analgesic drugs 304
Partnership of patients, pharmacists and companies 305
Factors that may influence future pain markets 305
Drivers of pain markets 305
Public surveys as indicators of impact of pain on people 305
Effect of regulatory reviews on markets for pain products 306
Novel versus older therapies for pain 306
9. Future of Pain Therapeutics 308
Introduction 308
Advances in the understanding of pain 308
Pathogenesis of chronic pain 308
Role of glia in neuropathic pain 308
Molecular and neurobiological techniques 309
Improved understanding of cancer pain 310
Advances in drug discovery and development for pain 310
Novel targets for drug discovery for pain 310
PTH2 receptor 310
Modulators of endogenous cannabinoids 311
Application of new technologies to pain therapeutics 311
Application of nanobiotechnology to pain therapeutics 312
Technologies for the manufacture of analgesics 313
Future trends and needs in pain management 313
Pain management in future healthcare systems 314
Systems biology approach to pain 314
Personalized pain management 315
Pharmacogenomics and pharmacogenetics of pain 316
Genetic mutations associated with reduced response to analgesics 317
Genetic mutations with loss of pain 317
Mechanism-specific management of pain 318
Preoperative testing to tailor postoperative analgesic requirements 318
Strategies for improving pain management 318
10. Companies Involved in Pain Therapeutics 320
Introduction 320
Profiles of companies 320
Collaborations 490
11. References 496
Tables
Table 1-1: Landmarks in the history of pain therapeutics 22
Table 1-2: Classification of pain 24
Table 1-3: Classification of neuropathic pain 26
Table 1-4: Classification of chronic cancer pain according to cause 27
Table 1-5: Percentage of patients with pain according to the type of cancer 28
Table 1-6: Key molecular elements of pain in the peripheral nervous system 50
Table 1-7: Key molecular elements of pain in the central nervous system 50
Table 2-1: IASP guidelines for the use of animals in pain studies 62
Table 2-2: Chronic pain as a manifestation of other diseases 63
Table 2-3: Recommendations for assessing patient satisfaction with pain management 68
Table 3-1: Classification of some currently used pain medications according to mechanism 75
Table 3-2: Drugs used for the treatment of pain 75
Table 3-3: Selective COX-2 inhibitors in clinical use for pain 77
Table 3-4: Antiepileptic drugs with analgesic effect 90
Table 3-5: Companies developing products to deter abuse of opioids 101
Table 4-1: Non-pharmacological approaches to management of pain 108
Table 4-2: Companies involved in neuromodulation therapy for pain 113
Table 4-3: Reasons for the inadequate management of acute pain 116
Table 4-4: Causes of chronic backache 132
Table 4-5: Management of chronic pelvic pain 134
Table 4-6: Management of pain in cancer 135
Table 4-7: Definitions of tolerance, physiological dependence, withdrawal and addiction 141
Table 4-8: A simplified classification of headache 141
Table 4-9: Various methods for the management of migraine 142
Table 4-10: Management of neuropathic pain based on mechanism and diagnosis 151
Table 4-11: Management of central neuropathic pain 154
Table 4-12: Current management of peripheral diabetic neuropathy 158
Table 4-13: Treatment strategies for postherpetic neuralgia 159
Table 4-14: Management of complex regional pain syndrome 161
Table 4-15: Methods of treating phantom limb pain 164
Table 4-16: Anti-itching therapies 170
Table 4-17: Suggested improvements in the management of pain 180
Table 5-1: A classification of drug delivery methods used in management of pain 181
Table 5-2: Selected marketed non-injection drug delivery systems for pain 185
Table 5-3: Spinal administration of drugs for pain 200
Table 5-4: Selected drug delivery systems for pain in clinical development 206
Table 6-1: Classification of drugs in development for pain 209
Table 6-2: Preclinical studies on cannabinoid (CB2) receptor agonists as analgesics 214
Table 6-3: Cannabinoid receptor agonists in clinical development as analgesics 215
Table 6-4: NO-related therapies for pain 232
Table 6-5: Major opioids receptors and their ligands 235
Table 6-6: Strategies to counteract pain at various levels at periphery and in the CNS 240
Table 6-7: Types of TRPV1 antagonists 242
Table 6-8: TRPV1 antagonists in clinical trials 242
Table 6-9: Experimental gene therapy approaches for relief of pain 249
Table 6-10: Selected preclinical approaches to pain therapy 257
Table 6-11: Selected preclinical drugs for neuropathic pain 258
Table 6-12: Selected clinical trials of miscellaneous drugs for pain 265
Table 6-13: Selected clinical trials of drugs for postsurgical pain 268
Table 6-14: COX-2 inhibitors in clinical development 270
Table 6-15: Disease modifying drugs for arthritis in clinical trials 271
Table 6-16: Clinical trials of drugs for neuropathic pain 272
Table 6-17: Selected drugs in clinical development for migraine 282
Table 6-18: Therapeutic targets for treating visceral pain 284
Table 8-1: Market values for various painful conditions 2009-2019 295
Table 8-2: Changes in market shares of drugs for neuropathic pain 2009-2019 297
Table 8-3: Markets for pain according to therapies 2009-2019 298
Table 8-4: Distribution of value of pain therapeutics in major markets 2009-2019 301
Table 8-5: Distribution of value of opioids in major pain markets 2009-2019 301
Table 8-6: Distribution of value of NSAIDs in major pain markets 2009-2019 301
Table 8-7: Strategies for developing pain markets 303
Table 9-1: P450 isoforms in the metabolism of drugs used in the management of pain 315
Table 10-1: Product pipeline of Adolor Corporation 325
Table 10-2: Selected collaborations in the area of pain management 489
Figures
Figure 1-1: Afferent pain pathways 30
Figure 1-2: Evolution of the gate control theory 32
Figure 1-3: The body self-neurometric 33
Figure 1-4: Various ligands and receptors on the peripheral terminals of nociceptive nerve fibers 50
Figure 1-5: Prostaglandin biosynthesis pathway 54
Figure 2-1: Biopsychosocial factors that interact and modulate the experience of pain 64
Figure 2-2: Pain intensity scales 65
Figure 4-1: The WHO step ladder for pain 136
Figure 4-2: An algorithm for the acute management of migraine 143
Figure 4-3: Neuroimmune activation events leading to sensitization of CNS 150
Figure 4-4: An algorithm for the management of peripheral neuropathic pain 163
Figure 4-5: Algorithm for management of patients with chronic pain and depression 167
Figure 5-1: Powder Injection Systems 192
Figure 6-1: Attributes of the ideal analgesic 210
Figure 6-2: Nerve targeting drug delivery system for gene therapy of pain 253
Figure 8-1: Unfulfilled needs in the treatment for chronic pain 302
Figure 9-1: Impact of new technologies on pain therapeutics 311
Figure 9-2: A scheme of personalized management of pain 314
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Drug and Medication Industry: Pain Therapeutics - Drugs, Markets and Companies
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Reportlinker |
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SOURCE Reportlinker
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