Reportlinker Adds Pain Therapeutics - Drugs, Markets and Companies

NEW YORK, June 3 /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 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 161 of these are profiled in the report along with 143 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 86

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 92

Phenytoin 93

Pregabalin 93

Topiramate 94

Valproic acid 94

Other antiepileptic drugs 94

Clonidine 95

Baclofen 95

Corticosteroids 95

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 101

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

Adverse effects of miscellaneous non-narcotic analgesics 103

Adverse effects of immunosuppressants used for relief of pain 104

Adverse effects of acetaminophen 104

4. Management of Pain 105

Introduction 105

Sites for pain management 105

Self-medication at home 105

Physicians' offices 105

Major hospitals 105

Pain centers 106

Non-pharmacological approaches to pain 106

Alternative medicine 106

Acupuncture 107

Aromatherapy 107

Self-Controlled Energo Neuro Adaptive Regulation 108

Behavioral therapy 108

Cognition and pain 108

Control over brain activation and pain by using functional MRI 108

Virtual reality therapy 109

Local application of heat 109

Transcutaneous nerve stimulation 109

Transcranial magnetic stimulation 110

Neurosurgery for pain relief 110

Ablative procedures on the nervous system 110

Procedures on peripheral, spinal and cranial nerves 110

Vagal nerve stimulation for control of pain 111

Neuromodulation 111

Spinal cord stimulation 112

Brain stimulation 112

Implantation of drug delivery devices 112

Management of special types of pain 113

Acute pain 113

Management of acute renal colic: NSAIDS vs. opioids 113

Combination of opioids and NSAIDs for acute pain 113

Reasons for inadequate management of acute pain 113

Perioperative pain management 114

Devices for delivery of analgesics in the postoperative period 114

Drug combination for perioperative pain 115

Gabapentin for reduction of postoperative pain 116

Ketamine for perioperative pain 116

Opioids for perioperative pain 116

Perioperative pain in neurosurgery 117

Prolonged duration local anesthesia 117

Pain in the intensive care unit 117

Pain associated with sports and exercise 118

Pain associated with trauma 118

Chronic abdominal pain 119

Functional somatic syndromes 119

Fibromyalgia syndrome 120

Pathomechanism of FMS 120

Management of FMS 120

New developments in pharmacotherapy of FMS 121

Erythromelalgia 122

Irritable bowel syndrome 122

Opioids for IBS 123

Tricyclic antidepressants for IBS 123

Serotonin-modulating drugs for IBS 123

Musculoskeletal pain 124

Myofascial pain syndrome 124

Osteoarthritis 125

Pathomechanism of osteoarthritis 125

Pain aggravates osteoarthritis by crosstalk between CNS and the joint 125

Management of osteoarthritis 126

Rheumatoid arthritis 127

Management of pain in rheumatoid arthritis 127

Disease modifying therapies in rheumatoid arthritis 128

Resurgence of interest in gold-based treatments for RA 128

Backache 129

Use of analgesics for management of back pain 130

Miscellaneous medical therapies for backache and sciatica 131

Neck pain 131

Chronic pelvic pain 131

Prostatitis 132

Cancer pain 132

Opioid treatment of cancer pain 133

Breakthrough and opioid-insensitive pains 134

Morphine-induced enhancement of cancer growth and its prevention 134

Methods of delivery of opioids for cancer pain 134

Implantation of drug delivery devices 135

Management of bone pain in cancer 135

Use of non-opioid analgesics for cancer pain 136

Adjuvant drugs for cancer pain 136

Radiation therapy 136

Alternative non-pharmacological methods 137

Anesthetic techniques 137

Surgical methods of cancer pain relief 137

Conclusions regarding management of cancer pain 137

Chronic non-malignant pain 138

Headache 138

Migraine 139

Management of acute migraine 139

Neurostimulation for migraine 143

Transcranial magnetic stimulation for migraine 144

Migraine prophylaxis 144

Cluster headache 144

Tension headache 145

Chronic daily headache 145

Trigeminal neuralgia 146

Dental pain 146

Neuropathic pain 146

Pathogenesis of neuropathic pain 147

Chronobiology of neuropathic pain as guide to therapy 147

Management of neuropathic pain based on mechanism 148

Guidelines for the management of neuropathic pain 148

Pharmacotherapy of neuropathic pain 149

Evidence-based management of neuropathic pain 151

Management of central neuropathic pain 151

Neurosurgical approaches to central neuropathic pain 152

Management of neuropathic pain in syringomyelia 152

Neuropathic pain associated with spinal cord injury 152

Peripheral neuropathic pain 153

Management of postsurgical peripheral neuropathic pain 153

Management of chemotherapy-induced pain 153

Morton's neuroma 154

Management of peripheral diabetic neuropathy 154

Postherpetic neuralgia 156

Complex regional pain syndrome 158

An algorithm for the management of peripheral neuropathic pain 159

Phantom limb pain 160

Pathomechanism of phantom limb pain 160

Management of phantom limb pain 161

Pain and depression 163

Neurochemical link between pain and depression 163

Management of chronic pain and depression 164

Miscellaneous painful conditions 165

Burning mouth syndrome 165

Chronic unstable angina 165

Mastalgia 165

Ophthalmic pain 166

Pain in Parkinson's disease 166

Management of itching 166

Topical applications for itching 167

Systemic therapies for itching 168

Non-pharmacological therapies for itch 169

Management of pain in special population groups 169

Racial and ethnic differences in pain management 169

Pain in neonates 169

Management of pain in children 170

Management of pain in the elderly 170

Management of pain in women 171

Reasons for increased pain perception in women 172

Chronic pelvic pain in women 172

Gender differences in response to analgesics 172

Considerations for pain management in women 173

Management of pain in neurologically handicapped persons 173

Management of pain in the cognitively impaired elderly people 173

Management of pain in brain-damaged minimally conscious patients 174

Management of pain in the terminally ill 174

Deficiencies in the management of pain 175

Negative physician attitudes in pain management 175

Suggestions for improvement of pain management by healthcare providers 176

Pain as the fifth vital sign 177

Multidisciplinary approaches to pain management 177

5. Drug Delivery for Pain 179

Introduction 179

Intra-articular injection for relief of joint pain 180

Controlled release drug delivery for pain 180

Accelerating the effect of subcutaneous morphine 180

Controlled drug delivery at site of pain 180

Oral extended release opioids 181

Extended release oral morphine 181

Controlled release oxycodone 182

Extended release oxymorphone 182

Oral extended release tramadol 182

Extended release gabapentin 183

Use of nanotechnology for drug delivery for pain 183

Non-injection methods of delivery of analgesics 183

Topical applications for pain 184

Topical local anesthetics 184

Topical NSAIDs 185

Topical and transdermal diclofenac 185

Topical application for postoperative pain 186

Needle-free drug delivery for pain 186

Glide SDI® solid dose injector 186

SUMAVEL™ DosePro™ needle-less injection 186

Transdermal drug delivery for pain 186

Relief of pain associated with minor medical procedures 187

Transdermal fentanyl 187

Transdermal ketoprofen 188

Transdermal nitroglycerine as an adjuvant to opioids 189

Transdermal buprenorphine 189

Transdermal trans-capsaicin 189

Powder Injection Systems 190

Intranasal delivery of analgesics 190

Intranasal morphine 190

Intranasal morphine derivatives 191

Intranasal fentanyl 192

Intranasal buprenorphine 192

Intranasal ketamine 192

Intranasal ketorolac 193

Nasal formulations for migraine 193

Oral spray formulations for migraine 193

Delivery of analgesics by inhalation 194

Buccal transmucosal and sublingual delivery of analgesics 194

Application for cancer pain 194

Application for non-cancer pain 195

Pumps for drug delivery in pain 195

Patient controlled analgesia 196

Postoperative pain pumps 196

Chronogesic (sufentanil) Pain Therapy System 197

Spinal pumps for delivery of analgesics 198

Spinal delivery of analgesics 198

Epidural dexamethasone 199

Perispinal etanercept 199

Intrathecal ziconotide 200

Intrathecal CGX1160 200

Intrathecal neostigmine 201

Intrathecal prostaglandin antagonists 201

Intrathecal non-NMDA antagonists 201

Intrathecal fadolmidine 201

Intrathecal resiniferatoxin 202

Concluding remarks on intrathecal delivery of analgesic agents 202

Intracerebroventricular morphine for pain 203

Development of drug delivery systems for pain therapy 203

Delivery of analgesics to the CNS across the blood brain barrier 203

Drug delivery systems in clinical trials 204

6. Drug Development for Pain 207

Introduction 207

Drugs in development for pain 207

Current research goals 208

The ideal analgesic 208

Pain R & D goals in the pharmaceutical industry 208

Drug targets in the spinal cord 209

Drug targets in the brain 209

Molecular targets for analgesic drugs 209

Activation of P2X7 receptors 209

Adenosine receptor agonists 210

Alfa2-adrenergic receptor agonists 210

Bradykinin antagonists 210

Cannabinoids 211

Cannabinoid receptor agonists 211

Cannabidiol 213

Cannabinor 214

Nabilone 214

Capsaicin and VR1 receptor-based analgesics 215

Vanilloid (capsaicin) receptor antagonists 215

VR1 receptor agonists 215

CCR2 receptor blockade 216

Cholecystokinin antagonists 216

Cholinergic receptor agonists 216

Conotoxins as analgesics 217

Corticotropin-releasing factor 218

FAAH inhibitors 218

PF-3845 219

URB597 219

Free radical scavengers as analgesics 219

Superoxide dismutase mimetics 220

GABA analogues 220

Subtype-selective GABAergic drugs 220

Glial cell line-derived neurotrophic factor 221

Glutamate receptor antagonists 221

NMDA receptor modulation for neuropathic pain 221

Alternatives to direct blocking of NMDA receptors 221

Glycine antagonists 222

Metabotropic glutamate receptors 222

Histogranin-like compounds for the management of pain 222

Ion channels as targets for analgesic drugs 223

Acid-sensing ion channels as drug target 223

Calcium channel blockers 224

P2X ion channel receptor antagonists 224

Sodium channel modulation 225

Microsomal prostaglandin E synthase inhibitors 225

NAALADase inhibitors 226

Nerve growth factor antagonists 226

Newer COX inhibitors 227

COX-3 inhibitors 227

Dual cyclooxygenase/lipoxygenase inhibitors 227

Neuropeptide receptor antagonists for improving the efficacy of opioids 228

Nicotinic acetylcholine receptors 228

Mode of action of nACh/neural nicotinic receptor agonists 228

Potential of central nACh/neural nicotinic receptor agonists 229

Nitric oxide-based analgesics 229

Nitric oxide-releasing NSAIDs 230

Pharmacology of NO-SAIDs 230

COX-inhibiting nitric oxide donors 231

NO-donating structures to extend life cycle of existing analgesics 231

Nitric oxide mimetics 231

Neuronal nitric oxide synthase inhibitors 232

Norepinephrine transporter inhibition 232

Opioid peptide receptors ligands 232

Buprenorphine 233

Nociceptin 234

Tapentadol 234

Opioid analgesics acting outside the CNS 235

Opioid analgesics acting at peripheral receptors 235

Peripherally acting mu-opioid receptor agonists 235

Targeting of opioid peptide-containing immune cells 235

Advantages of peripherally selective opioid drugs 236

Resolvins 236

Somatostatin analogs 236

Substance P and neurokinin receptor antagonists 237

Substance P-Saporin 237

Targeting prostanoid synthesis 238

Tetrodotoxin based analgesics 238

TRPV1 antagonists 239

TRPV1 antagonists in clinical trials 239

TRPV1-mediated entry of sodium channel blocker QX-314 240

Tumor necrosis factor-? antagonists 241

Cell and gene therapies for pain 241

Cell therapy 241

Implantation of chromaffin cells 241

Role of stem cells in management of pain 242

Implantation of astrocytes secreting enkephalin 243

Cells for delivery of antinociceptive molecules 243

Implantation of genetically engineered cells 243

Cell therapy for low back pain 244

Cell therapy for knee pain due to degenerative disorders 244

Cell therapy for peripheral neuropathy 245

Concluding remarks on cell therapy for pain 245

Gene therapy 245

Rationale of gene therapy for pain 246

Vectors for gene therapy of pain 246

Methods of gene delivery for pain 247

Vectors for endogenous analgesic production in cranial neuralgias 247

Gene delivery by intrathecal route 248

Gene transfer to the dorsal nerve roots 248

Gene therapy of peripheral neuropathy 249

Gene transfer by injections into the brain substance 250

Zinc finger DNA-binding protein therapeutic for chronic pain 250

Gene therapy for producing enkephalin to block pain signals 250

Targeting nuclear factor-?B 251

Gene therapy targeted to neuroimmune component of chronic pain 251

Antisense therapy for pain 252

RNAi-based approaches for pain therapy 252

Potential applications of gene therapy for management of pain 253

Concluding remarks about gene therapy for pain 253

Preclinical development of pain drugs 254

NGF-blocking antibody 255

Prostatic acid phosphatase as a novel analgesic 255

Preclinical development of drugs for neuropathic pain 255

5-HT receptor agonists 257

A-803467 257

AM1241 257

Artemin/Neuroblastin 257

Capsazepine 258

Central nACh receptor agonists 258

CGP 35024 259

Drugs that suppress glial activation 259

Erythropoietin 259

Gene therapy for neuropathic pain 260

NCX 8001 260

NR2B subtype NMDA receptor ligands 261

NW-1029 261

R116301 261

Targeting tumor necrosis factor 261

Future targets for osteoarthritic pain 262

Pain drugs in clinical trials 262

Clinical trials of miscellaneous drugs for pain 262

Alvimopan 264

Asimadoline 265

EN3202 265

Oxytrex 265

Drugs in clinical trials for postsurgical pain 266

Bicifadine 266

DepoMorphine 267

TC-2696 268

Cox-2 inhibitors in clinical trials 268

Clinical trials of disease modifying therapies for rheumatoid arthritis 268

Drugs in clinical development for neuropathic pain 269

Adenosine A1 agonists for neuropathic pain 272

Botulinum toxin type A 272

CPL7075 273

D-amino acid oxidase inhibitors 273

Glyx-13 273

IP-751 274

Lacosamide 274

Oxcarbazepine 275

Perampanel 275

Ralfinamide 275

Retigabine 275

SB-509 276

SCP-1 276

TC-6499 276

Tebanicline 276

Tezampanel 277

Thalidomide 277

TRO19622 277

V3381 (indantadol) 278

XP-13512 278

Zonisamide 278

Drug discovery and development for migraine 279

Drugs in clinical development for migraine 279

Drug development for visceral pain 282

7. Legal and regulatory issues of pain management 283

Pain relief as a legal right 283

Pain relief and the WHO 283

Regulatory issues 283

Opioids and cannabinoids 283

DEA and use of opioids for pain relief in terminal care 283

FDA and COX-2 inhibitors 284

Legal issues of COX-2 inhibitors 285

Regulatory issues of opioid safety 285

Opioid misuse and regulatory agencies 285

FDA measures for safety of opioid use 285

Misuse of fentanyl 286

8. Pain Markets 287

Introduction 287

Epidemiological basis of pain markets 287

Cancer 288

Neuropathic pain 288

Trigeminal neuralgia 288

Arthritis 288

Backache 288

Migraine 289

Multiple sclerosis 289

Irritable bowel syndrome 289

Chronic pelvic pain 289

Chronic pain due to traumatic brain injury 289

Postsurgical pain 290

Economics of pain 290

Pain as a driver of healthcare costs 290

Disability and financial loss through pain 291

Pain markets based on painful conditions 291

The cancer pain market 291

The arthritis pain market 292

Postsurgical pain market 292

The backache market 292

The headache market 293

Neuropathic pain market 293

Fibromyalgia market 294

Pain markets based on drugs 294

Opioids 294

Nonsteroidal antiinflammatory drugs 294

Transdermal pain therapeutics 295

Anesthesia 295

Antiepileptic drugs as analgesics 295

Other drugs 296

Hospital vs retail share of pain market 296

Hospital versus retail opioid market 296

Devices for pain 296

Pain markets according to geographical areas 296

Cost effectiveness of various approaches 297

Unfulfilled R&D needs in pain therapy 297

Under treatment of pain 297

Unfulfilled needs in drug development for chronic pain 298

Strategies for developing pain markets 298

Finding alternatives to intrathecal administration for chronic pain 299

Development of other applications of analgesic drugs 299

Partnership of patients, pharmacists and companies 300

Factors that may influence future pain markets 300

Drivers of pain markets 300

Public surveys as indicators of impact of pain on people 300

Effect of regulatory reviews on markets for pain products 301

Novel versus older therapies for pain 301

9. Future of Pain Therapeutics 303

Introduction 303

Advances in the understanding of pain 303

Pathogenesis of chronic pain 303

Role of glia in neuropathic pain 303

Molecular and neurobiological techniques 304

Improved understanding of cancer pain 305

Advances in drug discovery and development for pain 305

Novel targets for drug discovery for pain 305

PTH2 receptor 305

Modulators of endogenous cannabinoids 306

Application of new technologies to pain therapeutics 306

Application of nanobiotechnology to pain therapeutics 307

Technologies for the manufacture of analgesics 308

Future trends and needs in pain management 308

Pain management in future healthcare systems 309

Systems biology approach to pain 309

Personalized pain management 310

Pharmacogenomics and pharmacogenetics of pain 311

Genetic mutations associated with reduced response to analgesics 312

Genetic mutations with loss of pain 312

Mechanism-specific management of pain 313

Preoperative testing to tailor postoperative analgesic requirements 313

Strategies for improving pain management 313

10. Companies Involved in Pain Therapeutics 315

Introduction 315

Profiles of companies 315

Collaborations 484

11. References 489

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 106

Table 4 2: Companies involved in neuromodulation therapy for pain 111

Table 4 3: Reasons for the inadequate management of acute pain 114

Table 4 4: Causes of chronic backache 129

Table 4 5: Management of chronic pelvic pain 131

Table 4 6: Management of pain in cancer 132

Table 4 7: Definitions of tolerance, physiological dependence, withdrawal and addiction 138

Table 4 8: A simplified classification of headache 138

Table 4 9: Various methods for the management of migraine 139

Table 4 10: Management of neuropathic pain based on mechanism and diagnosis 148

Table 4 11: Management of central neuropathic pain 151

Table 4 12: Current management of peripheral diabetic neuropathy 155

Table 4 13: Treatment strategies for postherpetic neuralgia 156

Table 4 14: Management of complex regional pain syndrome 158

Table 4 15: Methods of treating phantom limb pain 161

Table 4 16: Anti-itching therapies 167

Table 4 17: Suggested improvements in the management of pain 177

Table 5 1: A classification of drug delivery methods used in management of pain 179

Table 5 2: Selected marketed non-injection drug delivery systems for pain 183

Table 5 3: Spinal administration of drugs for pain 198

Table 5 4: Selected drug delivery systems for pain in clinical development 204

Table 6 1: Classification of drugs in development for pain 207

Table 6 2: Preclinical studies on cannabinoid (CB2) receptor agonists as analgesics 212

Table 6 3: Cannabinoid receptor agonists in clinical development as analgesics 213

Table 6 4: NO-related therapies for pain 229

Table 6 5: Major opioids receptors and their ligands 233

Table 6 6: Strategies to counteract pain at various levels at periphery and in the CNS 238

Table 6 7: Types of TRPV1 antagonists 239

Table 6 8: TRPV1 antagonists in clinical trials 240

Table 6 9: Experimental gene therapy approaches for relief of pain 247

Table 6 10: Selected preclinical approaches to pain therapy 254

Table 6 11: Selected preclinical drugs for neuropathic pain 256

Table 6 12: Selected clinical trials of miscellaneous drugs for pain 262

Table 6 13: Selected clinical trials of drugs for postsurgical pain 266

Table 6 14: COX-2 inhibitors in clinical development 268

Table 6 15: Disease modifying antirheumatic drugs in clinical trials 268

Table 6 16: Clinical trials of drugs for neuropathic pain 270

Table 6 17: Selected drugs in clinical development for migraine 279

Table 6 18: Therapeutic targets for treating visceral pain 282

Table 8 1: Market values for various painful conditions 2009-2019 291

Table 8 2: Changes in market shares of drugs for neuropathic pain 2009-2019 293

Table 8 3: Markets for pain according to therapies 2009-2019 294

Table 8 4: Distribution of value of pain therapeutics in major markets 2009-2019 297

Table 8 5: Distribution of value of opioids in major pain markets 2009-2019 297

Table 8 6: Distribution of value of NSAIDs in major pain markets 2009-2019 297

Table 8 7: Strategies for developing pain markets 299

Table 9 1: P450 isoforms in the metabolism of drugs used in the management of pain 311

Table 10 1: Product pipeline of Adolor Corporation 321

Table 10 2: Endo Pharmaceuticals' products in clinical trials 375

Table 10 3: Selected collaborations in the area of pain management 484

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 133

Figure 4 2: An algorithm for the acute management of migraine 140

Figure 4 3: Neuroimmune activation events leading to sensitization of CNS 147

Figure 4 4: An algorithm for the management of peripheral neuropathic pain 160

Figure 4 5: Algorithm for management of patients with chronic pain and depression 164

Figure 5 1: Powder Injection Systems 190

Figure 6 1: Attributes of the ideal analgesic 208

Figure 6 2: Nerve targeting drug delivery system for gene therapy of pain 250

Figure 8 1: Unfulfilled needs in the treatment for chronic pain 298

Figure 9 1: Impact of new technologies on pain therapeutics 307

Figure 9 2: A scheme of personalized management of pain 310

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Drug and Medication Industry: Pain Therapeutics - Drugs, Markets and Companies

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Nicolas Bombourg

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