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Pain Therapeutics - Drugs, Markets and Companies

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

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

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

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

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

Over 500 companies have been identified to be involved in developing or marketing pain therapeutics and 166 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 2012 and projected to 2022. 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 66 tables, 18 figures, and 600 selected references to the literature.

Table of Contents

0. Executive Summary ........ 17
1. Basic Aspects of Pain ...... 19
Introduction ........ 19
Historical aspects of pain ......... 19
Pain definitions .... 21
A glossary of terms relevant to pain .. 22
Pain classification and description ..... 22
Neuropathic pain 23
Refractory neuropathic pain ......... 24
Classification of neuropathic pain according to levels ..... 24
Cancer pain ....... 25
Bone pain in cancer . 27
Complex regional pain syndrome ....... 27
Mechanisms of pain ....... 28
Pain pathways ... 28
Role of nociceptors in pain transmission ... 30
Gate control and neuromatrix theories of pain ......... 30
Pain mediators .. 31
Modulation of pain by pictures associated with social contacts ....... 32
Modulation of pain by emotions ......... 32
Role of the sympathetic nervous system in pain ....... 32
Visceral pain...... 32
Pathomechanism of visceral pain .. 33
Pathomechanism of neuropathic pain . 33
Role of intact nerve fibers in neuropathic pain .... 33
Chemokines as mediators of neuropathic pain .... 33
Chemotherapy-induced neuropathic pain . 34
CNS innate immunity and neuropathic pain ........ 34
Cytokines as mediators of neuropathic pain ........ 34

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Pain Therapeutics - Drugs, Markets and Companies


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