Peripheral neuropathic pain

Stacey BR. Management of peripheral neuropathic pain. AmJPhysMedRehabil. 2005 84(suppl) S4-S16. 

Thacker, M. A., Clark, A. K., Marchand, F., and McMahon, S. B. (2007). Pathophysiology of peripheral neuropathic pain Immune cells and molecules. Anesth. Analg. 105, 838-847. 

Hansson P T, Dickenson A H (2005). Pharmacological treatment of peripheral neuropathic pain conditions based on shared commonalities despite multiple etiologies. Pain. 113 251-254. 

Duloxetine (Fig. 21.18) has been approved for the treatment of depression and diabetic peripheral neuropathic pain. It is another analogue in the line of fluoxetine-based products from Lilly, in which the... 

Jensen TS, Backonja M, Jimenez SH et al. New perspectives on the management of diabetic peripheral neuropathic pain. Diabet Vase Dis Res 2006 3(2) 108-119. 

Examples of cutaneous patches are lidocaine containing patches that sometimes contain a second local anaesthetic. After applying the patch, lidocaine penetrates deep into the skin where it has a local anesthetising effect. Capsaicin containing patches are used in the treatment of peripheral neuropathic pain in non-diabetic adults. Following exposure to the patch, capsaicin penetrates the skin and interacts with the cutaneous transient receptor potential vanilloid 1 receptor (TRPVl) resulting in pain relief. 

A comprehensive set of practice parameters on the use of spinal cord stimulation in the treatment of chronic neuropathic pain has been developed [42]. Indications include failed back surgery syndrome, complex regional pain syndrome, peripheral neuropathic pain, phantom limb/post-amputation syndrome, recalcitrant PHN, root injury pain, and spinal cord injury or lesions. It also is being used in the management of pain associated with multiple sclerosis, pain due to ischemic peripheral vascular disease, and interstitial nephritis. 

Diabetic peripheral neuropathic pain patients may start duloxetine with 60 mg or a lower dose and gradually titrate due to the concern of common renal insufficiency in patients with diabetes. 

Diabetic peripheral neuropathic pain the effectiveness of duloxetine must be assessed carefully based on the progress of diabetic peripheral neuropathy. 

The efficacy of duloxetine in pain management of diabetic peripheral neuropathy was recognized in two randomized, 12-week, double-blind, placebo-controlled, fixed-dose studies. These were adult patients with at least 6 months history of peripheral neuropathic pain due to diabetes. 

ER) for diabetic peripheral neuropathic pain results of a randomized-withdrawal, double-blind, placebo-controlled phase III Study. Poster presented at the 61st Annual Meeting of the American Academy of Neurology (AAN) April 25-May 2,... 

Babbar S, Marier JF, Bley K. Pharmacokinetic analysis of capsaicin after topical administration of a high-concentration capsaicin patch to patients with peripheral neuropathic pain. NeurogesX inc, San Mateo, California 94404, USA. 

Ogawa S, Satoh J, Arakawa A, Yoshiyama T, Suzuki M. Pregabalin treatment for peripheral neuropathic pain a review of safety data from randomized controlled trials conducted in Japan and in the west. Drug Saf October 1, 2012 35(10) 793-806. 

Antiepileptics are used in neuropathic pain resulting from lesions to the peripheral (e.g., diabetes, heipes) or central nervous system (e.g., stroke). Such syndromes have been attributed to ectopic activity in sensitized nociceptors from regenerating nerve sprouts, recruitment of previously silent nociceptors, and/or spontaneous neuronal activity. This may result in sensitization... 

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

The amide local anaesthetic lidocaine may also be used as an antianhythmic for ventricular tachycardia and exra-systoles after injection into the blood circulation. Drugs with high lipid solubility such as bupivacaine cannot be used for these purposes because their prolonged binding to the channel may induce dysrhythmias or asystolic heart failure [3]. Systemically applied lidocaine has also been used successfully in some cases of neuropathic pain syndromes [4]. Here, electrical activity in the peripheral nervous system is reduced by used-dependent but incomplete sodium channel blockade. 

Neuropathic pain is initiated or caused by a primary lesion in the peripheral or central nervous system. The causative agent may be trauma, nerve-invading cancer, herpes zoster, HIV, stroke, diabetes, alcohol or other toxic substances. Neuropathic pain is refractory to most analgesic drugs. Altered sodium channel activity is characteristics of neuropathic pain states. 

Fig. 4.1 Hypothetical model of pathogenesis of pain in DSP. (1) Injury of peripheral nerve fibers due to multifocal inflammation and secreted macrophage activation products results in abnormal spontaneous activity of neighboring uninjured nociceptive fibers ( peripheral sensitization ). (2) Furthermore, the aberrant inflammatory response in DRG leads to alterations in neuronal sodium and calcium channel expression and ectopic impulse generation. (3) This results in central remodeling within the dorsal horn due to A-fiber sprouting and synaptic formation with pain fibers in lamina 11, and maintenance of neuropathic pain ( central sensitization ). Reproduced with permission from (Keswani et al. 2002)...

Herzberg U, Sagen J (2001) Peripheral nerve exposure to HIV viral envelope protein gpl20 induces neuropathic pain and spinal gliosis. J Neuroimmunol 116(l) 29-39 Herzmann C, Johnson MA et al (2005) Long-term effect of acetyl-L-carnitine for antiretroviral toxic neuropathy. HIV Clin Trials 6(6) 344-350... 

Sweitzer SM, Hickey WF et al (2002) Focal peripheral nerve injury induces leukocyte trafficking into the central nervous system potential relationship to neuropathic pain. Pain 100(1-2) 163-170... 

In the peripheral nervous system (PNS), HIV-1 infection and its treatment using HAART are associated with the development of neuropathic pain syndromes characterized by severe lancinating pain as well as parathesias and burning pain in the extremities. Damage to peripheral nerves has been associated with these syndromes. HIV-1-associated polyneuropathy has become the most common neurological complication of HIV-1 infection (Pardo et al. 2001). More than half of individuals with... 

Pain sensation is modulated by glial cells communication with neuronal cells (reviewed by Scholz and Woolf 2007). The involvement of the CX3CL1/CX3CR1 pair in pain modulation has been recently demonstrated in different examples of experimental neuropathic pain induced by peripheral nerve injury or inflammation... 

The mechanisms of pain and the ability to control pain may vary in different pain states. This is of particular importance in consideration of a rational basis for the treatment of both inflammatory and neuropathic pain where the damage to tissue and nerve leads to alterations in both the peripheral and central mechanisms of pain signalling. In respect of existing drug therapies, this plasticity, the ability of the system to change in the face of a particular pain syndrome, explains the effectiveness of NSAIDs in inflammatory conditions and yet is also responsible for some of the limitations in the effectiveness of opioids in neuropathic pain. 

Neuropathic pain states are thought to be generated in the peripheral sensory neurons by events within the nerve itself and so are independent of peripheral nociceptor activation. Damage to peripheral nerves can be caused by a number of pathological, metabolic and viral causes. According to the terminology guide of the International... 

Association of Pain, neuropathic pain is defined as pain initiated or caused by a primary lesion, dysfunction in the nervous system". Neuropathy can be divided broadly into peripheral and central neuropathic pain, depending on whether the primary lesion or dysfunction is situated in the peripheral or central nervous system. In the periphery, neuropathic pain can result from disease or inflammatory states that affect peripheral nerves (e.g. diabetes mellitus, herpes zoster, HIV) or alternatively due to neuroma formation (amputation, nerve transection), nerve compression (e.g. tumours, entrapment) or other injuries (e.g. nerve crush, trauma). Central pain syndromes, on the other hand, result from alterations in different regions of the brain or the spinal cord. Examples include tumour or trauma affecting particular CNS structures (e.g. brainstem and thalamus) or spinal cord injury. Both the symptoms and origins of neuropathic pain are extremely diverse. Due to this variability, neuropathic pain syndromes are often difficult to treat. Some of the clinical symptoms associated with this condition include spontaneous pain, tactile allodynia (touch-evoked pain), hyperalgesia (enhanced responses to a painful stimulus) and sensory deficits. 

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