Systemic injections of TTX diminished pain behaviour in a dose-dependent manner in models of inflammatory, visceral and neuropathic pain without causing adverse events, whereas morphine analgesia was associated with heavy sedation. TTX is a very promising substance for the treatment of various types of pain but needs further evaluation.
Pain is an unpleasant sensation that originates from ongoing or impending tissue damage. Management of different types of pain (acute, postoperative, inflammatory, neuropathic or cancer) is the most frequent issue encountered by clinicians and pharmacological therapy is the first line of approach for the treatment of pain. This review presents and discusses recent clinical advances regarding both the improvements in delivery of analgesic drugs and improvements in the design of analgesic molecules. The new modalities of administration of analgesics used in the clinic are reviewed, including skin patches, oral and mucosal sprays, transdermal delivery systems and intranasal administration. New insights are then presented on standard drugs used to relieve pain, such as opioids (including tramadol), NSAIDs including selective cyclo-oxygenase-2 inhibitors, paracetamol (acetaminophen), local anaesthetics and adjuvant analgesics such as antidepressants, anticonvulsants (gabapentin and pregabalin), cannabinoids, ketamine and others (e.g. nefopam). Although the understanding of pain mechanisms has improved significantly recently, much more is yet to be discovered and awaited. Broadening of our knowledge is needed to improve basic and clinical research in this field in order to better alleviate pain in millions of people.
Neuropathic pain is one of the most inextricable problems encountered in clinics, because few facts are known about its etiology. Nerve injury often leads to allodynia and hyperalgesia, which are symptoms of neuropathic pain. The aim of this study was to understand some molecular and electrophysiological mechanisms of neuropathic pain after chronic constriction of the saphenous nerve (CCS) in mice. After surgery, CCS mice displayed significant allodynia and hyperalgesia, which were sensitive to acute systemic injection of morphine (4 mg/kg), gabapentin (50 mg/kg), amitriptyline (10 mg/kg), and the cannabinoid agonist WIN 55,212-2 (5 mg/kg). These behavioral changes were accompanied after surgery by an increase of c-Fos expression and by an overexpression of mu-opioid and cannabinoid CB1 and CB2 receptors in the spinal cord and the dorsal hind paw skin. In combination with the skin-nerve preparation, this model showed a decrease in functional receptive fields downstream to the injury and the apparition of A-fiber ectopic discharges. In conclusion, CCS injury induced behavioral, molecular, and electrophysiological rearrangements that might help us in better understanding the peripheral mechanisms of neuropathic pain. This model takes advantage of the possible use in the future of genetically modified mice and of an exclusively sensory nerve for a comprehensive study of peripheral mechanisms of neuropathic pain.
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