Reportlinker Adds Pain Therapeutics - Drugs, Markets and Companies

Dec 21, 2010, 11:57 ET from Reportlinker

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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