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A Alpha- (ALA) , 91, 123 Acceptance and commitment therapy Alternative treatments (ACT) , 75, 76, 78 CAM, western society , 84 Acetyl L -carnitine (ALC) , 91, 129 mind-body therapies , 89–91 ACT. See Acceptance and commitment nutraceuticals therapy (ACT) ALA , 91 Acupuncture ALC , 91 alternative medicine techniques , 85 benfotiamine , 91 chemotherapy-induced peripheral fatty acids , 92 neuropathy , 89 B12 de fi ciency , 92 Chinese medicine , 84 zinc , 92 description , 66 osteopathic medicine , 83 DPN patients , 187–188 stimulation-based therapies moxibustion , 86 (see Acupuncture) multicenter randomized controlled traditional medicine , 83 trial , 88–89 American Diabetes Association (ADA) , needles , 86 194–195 receptors and endorphins , 85 Amyotrophy serotonin receptors , 85 asymmetrical proximal leg side effects , 88 weakness , 162 TCM , 86, 88 DPN , 162 timeline , 86, 87 ESR , 162 Acute painful neuropathy MRI, CT/ultrasound , 162 poor glycaemic control , 157 pain , 162 rapid glycaemic control (insulin ) , type 1 and type 2 diabetic patients , 162 157–158 , DPN transient neuropathic syndromes , 157 adverse event related withdrawal , Advanced practice registered nurses 178–179 (APRNs) , 142 effects, quality of life and physical ALA. See Alpha-lipoic acid (ALA) functioning , 178 ALC. See Acetyl L -carnitine (ALC) ef fi cacy, individual , 178 Aldose reductase inhibitors (ARI) , 128 epilepsy , 177 Allodynia , 17–19 impacts , 179 Alpha-2-delta ligand agonist antiepileptic inhibition , 177 drugs , 52–53 literature review , 177

E. Lawson and M. “Misha” Backonja (eds.), Painful Diabetic Polyneuropathy: 197 A Comprehensive Guide for Clinicians, DOI 10.1007/978-1-4614-6299-6, © Springer Science+Business Media New York 2013 198 Index

Antidepressants, DPN RCT , 74 adverse event related withdrawal , 176 Community depression , 174 activity , 142 ef fi cacy , 176 health care , 149, 150 impacts , 177 housing , 142 individual ef fi cacy , 175, 176 older adults , 144 SNRIs , 175 retirement , 143 TCAs , 175–176 Complementary and alternative medicine typical and atypical groups , 175 (CAM) Antiepileptic drugs , 53 mindful and meditative therapies , 89 APRNs. See Advanced practice registered organization , 84 nurses (APRNs) osteopathic manipulative treatment , 83 ARI. See Aldose reductase inhibitors (ARI) western society , 84 Asymmetrical neuropathies Cornal confocal microscopy (CCM) , 31 cranial mononeuropathy , 163 Cranial neuropathies , 163 diabetes , 162 pressure palsies (see Pressure palsies) proximal motor/amyotrophy , 162 D truncal radiculopathy , 163 Descending inhibition , 21 Diabetes mellitus description , 13 B insulin treatment , 39 Balneotherapy , 65 metabolic disorders , 155 Benfotiamine , 91 (DN) ALC , 91 asymmetrical (see Asymmetrical C neuropathies) Calcium channel modulators , 124–125 benfotiamine , 91 CAM. See Complementary and alternative CAM , 84 medicine (CAM) chronic pain , 90 , 182–183 clinical presentations , 130 Capsaicin , 54, 66, 126, 183 , 131 Capsaicin dermal patch fatty acids , 92 complications , 100 insensitivity and weakness , 155 FDA , 98 long-term complications , 155 PGIC , 99 management, patients , 131, 132 procedure , 99 mononeuropathy , 28 TRPV-1 , 98, 99 neurodegeneration , 14 , 31 , 49–50 Carpal tunnel syndrome , 163 painful and painless , 14 CBT. See Cognitive behavioral therapy (CBT) painful symptoms , 155 CCM. See Cornal confocal microscopy (CCM) pharmacological treatments CDC. See Centers for disease control and (see Pharmacological treatments) prevention (CDC) physical and mental QOL , 121 Centers for disease control and prevention polyneuropathy , 28 (CDC) , 194 side effects , 131, 133 Central nervous system (CNS) symmetrical (see Symmetrical painful neuropathy , 21 neuropathies) zinc , 92 symptoms , 122 Central sensitization , 52 trial design , 131 Chronic hyperglycemia , 39, 40 vitamin B12 de fi ciency , 92 Cognitive behavioral therapy (CBT) zinc , 92 ACT , 75 Diabetic painful neuropathy (DPN). neuropathic pain , 74 See Painful diabetic neuropathy psychological treatment methods , 73 (PDN) Index 199

Diabetic (DPN) DN. See Diabetic neuropathy (DN) acute hyperglycemia/insulin therapy , 38 DPN. See Diabetic peripheral neuropathy chronic , 160 (DPN) diagnosis , 157–158 Drugs, DPN direct medical costs , 108–111 anticonvulsants (see Anticonvulsants, drug therapy , 157 DPN) epidemiology , 108, 158–159 antidepressants (see Antidepressants, foot ulcer , 157 DPN) health status and functioning , 111–114 cannabinoids , 182–183 hyperglycemia , 107 ion channel blockers , 181–182 implications, clinicians , 115–116 NMDA antagonists , 182 interventional therapies , 95, 102 , 180 Melzack–Wall gate theory , 96, 97 topical analgesics (see Topical analgesics, modalities , 157 DPN) MRI , 156–157 , 181 nerve fi bers , 37 nociceptive neurons , 99 nursing and home care (see Nursing and E home care, PDPN) Electromagnetic therapy, DPN , 187 pain and metabolic control , 40 Electrotherapy, DPN pain assessment , 161–162 magnetic , 187 pathogenesis , 38 natural electricity , 185 pDPN , 115 pain management , 186 peripheral neutropathy and metabolic TENS , 186 control , 38–40 Epidemiology, PDN preventive and therapeutic strategies , de fi nition , 3–4 42–45 glycemic control , 8 Romberg’s sign , 157 health care burden , 5–6 screening , 41–42 length-dependent polyneuropathy , 4 sleep deprivation , 157 long-term longitudinal data , 7 small fi bers , 37 microvascular complications , 5 symmetrical and asymmetrical National Diabetes Fact Sheet , 2011, 7 neuropathies , 37, 38 nonmonetary burdens , 6–7 symptoms , 156 non-neuropathy pain , 4 unpleasant sensory symptoms , 157 pain and diabetic neuropathy , 4 work productivity , 114–115 Erythrocyte sedimentation rate (ESR) , 162 Diagnosis, PDN ESR. See Erythrocyte sedimentation rate carbamazepine , 31 (ESR) clinical presentation Exercise therapy , 64 “dying-back” , 27–28 “glove-and-stocking” , 28 non-neuropathic pain disorders , 29 F NPQ , 29 Fatty acids , 92 physical examination , 28 Food and Drug Administration (FDA) , 98, 100 screening tools , 28–29 Frequency-modulated electromagnetic neural symptoms , 28 stimulation (FREMS) , 187 types, neuropathy , 27, 28 con fi rmatory tests , 29–31 neuropathies , 32 G objective tests , 30, 33 GABA. See Gamma-aminobutyric acid Direct costs , 111 (GABA) Disease-modifying therapies , 52, 53, 56 ALA , 123 Gamma-aminobutyric acid (GABA) , 96 glycemic control , 122 Gamma-linolenic acid (GLA) , 92 200 Index

Gene therapy , 129 L GLA. See Gamma-linolenic acid (GLA) Laser Doppler imager (LDI) fl are , 30–31 Glyceryl trinitrate (GTN) spray, DPN , 183 Laser therapy , 65 Graded exposure, PDN , 76 , 53–54, 126

H M HADS. See Hospital anxiety and depression Magnetic fi eld therapy , 64–65 scale (HADS) MBSR. See Mindfulness based stress Health status , 111–114 reduction (MBSR) HFEN. See High-frequency external muscle Medical training therapy , 64 stimulation (HFEN) Melzack–Wall gate theory , 96, 97 High-frequency external muscle stimulation Metabolic control (HFEN) , 187 microvascular complications , 41 Hospital anxiety and depression scale pain , 40 (HADS) , 162 and peripheral neutropathy (see Peripheral Hyperalgesia neutropathy) ameliorate behavioral , 20 Mind-body therapies diabetic rats/mice , 18 ACT , 91 endogenous insulin/receiving insulin CAM treatments , 89 supplementation , 17 MBSR , 91 thermal hypoalgesia , 17 meditation, relaxation and yoga , 89, 90 TRPV4 receptor , 18 pain diagnoses , 91 Hyperglycemia , 107 PMR and autogenic training , 91 Hypnosis , 77 Mindfulness-based methods , 77–78 Mindfulness based stress reduction (MBSR) , 146 I Monoamine oxidase inhibitors (MAOIs) , 175 IENFD. See Intra-epidermal nerve fi ber density (IENFD) Indirect costs , 114, 115 N Insulin therapy , 14, 45 National Institute of Diabetes and Digestive Interventional therapies and Kidney Diseases (NIDDK) , 193 dorsal column SCS ( see Spinal cord National Institutes of Health (NIH) , 193–194 stimulation (SCS)) NCS. See Nerve conduction studies (NCS) DPN , 95 NDS. See Neurological disability score (NDS) high concentration capsaicin dermal Nerve conduction studies (NCS) , 29, 30 patch , 98–100 Neurodegeneration , 18 IT therapy , 100–102 Neurodegenerative disorders , 129 Intra-epidermal nerve fi ber density (IENFD) , Neurological disability score (NDS) , 14 30, 31 Neuropathic pain , 3–4, 49–50 Intrathecal (IT) therapy Neuropathic Pain Questionnaire (NPQ) , 29 infectious pathogen , 102 Neuropathic Pain Symptom Inventory (NPSI) , , 100 29, 33 procedure description , 101–102 Neuropathic ulcers , 63 pump placement , 102 Neuropathic vs. non-neuropathic pain , 72–73 SAE , 101 NIDDK. See National Institute of Diabetes , 100, 101 and Digestive and Kidney Diseases Ion channel blockers , 181–182 (NIDDK) Isosorbide dinitrate spray , 183 NIDDM. See Non-insulin-dependent diabetes IT therapy. See Intrathecal (IT) therapy mellitus (NIDDM) Index 201

NIH. See National Institutes of Health (NIH) pain management , 149 N -Methyl- D -Aspartate (NMDA) receptor PDPN risk , 142, 143 antagonists , 128–129, 182 polypharmacy , 144, 145 Nociceptor activation , 18 Opioid agonists , 55 Nociceptor activity , 19 Opioids, DPN Non-insulin-dependent diabetes mellitus acute and cancer pain management , 180 (NIDDM) , 167 tramadol, noradrenalin and serotonin Non-pharmacological management, PDN reuptake inhibitor , 181 acupuncture , 187–188 chronic pain , 188 complementary treatments, long-term P pain , 188 Pain electromagnetic therapy , 187 acupuncture , 89 electrotherapy , 185–186 CAM , 84 HFEN , 187 chronic , 89 literature review , 188 de fi nition , 37 magnetic therapy , 188 diabetic rodents , 16–17 PENS , 186–187 epidemiologic data , 3–4 photon stimulation , 188 MBSR , 146 spinal cord stimulation , 187 metabolic control , 40 TENS , 186 mind–body interventions , 91 Nonsterodial anti-in fl ammatory drugs neuropathy (NSAIDs) , 168 epidemiological study , 14 Novel imaging techniques , 122 hyperglycemia , 15 NPQ. See Neuropathic Pain Questionnaire insulin therapy , 14 (NPQ) lifestyle intervention , 14–15 NPSI. See Neuropathic Pain Symptom NDS , 14 Inventory (NPSI) nerve biopsy , 14 NSAIDs. See Nonsterodial anti-in fl ammatory nerve degeneration , 15 drugs (NSAIDs) non-neuropathy , 4 Nursing and home care, PDPN nursing care advanced practice , 149 neuropathic , 145 aging and diverse population , 149, 150 nociceptive , 145 APRNs , 142 pathogenesis , 38 barriers , 148–149 PDPN cost estimation , 142 characteristics , 145 educational preparation , 141–142 numeric rating scale (NSR) , 146 examination , 142 pharmacological treatment , 145–146 health care system , 149 symptoms , 146 implications , 149 post-herpetic neuralgia , 6 obesity, T2DM , 141 pro-in fl ammatory molecules , 18 objectives , 142 symptoms , 3 pain ( see Pain) VAS , 42 QOL (see Quality of life (QOL), DPN) Pain assessment, DPN safety (see Safety, PDPN) diagnosis , 160 sleep (see Sleep) HADS , 161 Nutraceuticals , 91–92 numeric rating scales (NRS) , 160 QoL , 160–161 therapies , 161 O Painful diabetic neuropathy (PDN) Older adult acupuncture , 66 exercise , 144 ALA , 16 longstanding diabetes , 141 alpha-2-delta ligand agonist antiepileptic mild cognitive impairment , 146 drugs , 52–53 202 Index

Painful diabetic neuropathy (PDN) (cont.) symptoms , 167 animal models treatment algorithm , 185, 189 CNS involvement , 21 Painful DPN (pDPN) pain, diabetic rodents , 16–17 health status , 107, 112–113 peripheral drive , 18–19 /gabapentin , 111 spinal ampli fi cation , 19–21 work-related impairments , 115 anticonvulsants and antidepressants , 16 Painful neuropathy treatment. See Diabetic antiepileptic drugs , 53 neuropathy (DN) balneotherapy , 65 Pain management. See Painful diabetic capsaicin , 54, 66 polyneuropathy (PDN) clinical strategies and personalized therapy , PARP. See Poly ADP-ribose polymerase 56–57 (PARP) diabetes and neuropathy , 13–14 Patient education DN and neuropathic pain , 49–50 American pain society web site , 194 drugs effective , 21–22 CDC , 194 duloxetine and pregabalin , 15 diabetes , 193 electrotherapy and magnetic fi eld therapy , evidence-based guideline, neurology , 194 64–65 Mayo clinic , 194 epidemiology (see Epidemiology, PDN) NIDDK and NIH , 193–194 exercise therapy and medical training Patient global impression of change therapy, 64 (PGIC) , 99 glucose metabolism , 22 Patient resources interventional therapy , 55–56 clinical trials , 195 laser therapy , 65 disease management and pain relief , 193 lidocaine , 53–54 education (see Patient education) medical therapies, neuropathic pain , 50, 51 support , 194–195 neuropathic ulcers , 63 web-based sources , 193 neuropathy and pain , 14–15 Patient support , 194–195 opioid agonists , 55 PDN. See Painful diabetic polyneuropathy pathogenic mechanism , 15 (PDN) peripheral neuropathy , 49 pDPN. See Painful DPN (pDPN) pharmacologic treatments , 67 Percutaneous electrical nerve stimulation psychological treatment (see Psychological (PENS) , 186–187 treatment) Peripheral nerve SNRIs , 52 impaired excitatory input , 20 symptoms , 63 neurodegeneration , 18 Tai Chi , 66 nociceptor activation , 18 TCAs , 51–52 nociceptor activity , 19 tramadol hydrochloride , 54–55 spinal sensitization mechanisms , 17 yoga , 66 Peripheral neutropathy Painful diabetic peripheral neuropathy autonomic symptoms , 40 (PDPN). See Interventional glyco-metabolic control , 38 therapies hyperglycemia , 38 Painful diabetic polyneuropathy (PDN) hypothesis derives , 38 antidepressants and anticonvulsants , 189 insulin neuritis , 39 impact, pain control and side effects prolonged oxidative stress , 39 management , 167 redox state , 39 NIDDM , 167 PGIC. See Patient global impression of change non-pharmacological (see Non- (PGIC) pharmacological management, Pharmacological management, PDN PDN) drugs (see Drugs, DPN) patient’s pain quality , 189 impacts, quality life and physical pharmacological management (see functioning , 174 Pharmacological management, pain control and side effects PDN) characteristics, studies , 170–173 Index 203

data analysis , 168 mindfulness-based methods , 77–78 eligibility studies , 168 neuropathic vs. non-neuropathic pain , identi fi cation and inclusion, studies , 72–73 168–169 pharmacological therapies , 72 literature review , 184 RCTs , 74 randomised trials , 168 relaxation training , 76–77 systematic review , 168 survey , 72 treatment period , 169, 174 “traditional CBT” , 78 qualities, pain , 184 treatment algorithm , 185 Pharmacological treatments Q ARI , 128 QoL. See Quality of life (QoL) C-peptide , 130 QTT. See Quantitative thermal thresholds disease-modifying therapies , 122–123 (QTT) gene therapy , 129 Quality of life (QoL) neurodegenerative disorders , 129 DPN patients , 174 NMDA , 128–129 physical and mental , 121 PARP , 130 pregabalin , 125 PKC inhibitors , 128 venlafaxine and duloxetine treatments , 124 symptomatic treatments (see Symptomatic Quantitative sensory tests , 42, 161 treatments) Quantitative thermal thresholds (QTT) , 30 taurine , 130 topical treatment , 129 Photon stimulation, DPN patients , 187–188 R Physical function treatment, DPN patients , Randomized controlled trials (RCTs) , 71, 74, 174 78, 124–126 Pittsburgh sleep quality index (PSQI) , 147 RCTs. See Randomized controlled trials PKC. See Protein kinase C (PKC) (RCTs) PMR. See Progressive muscle relaxation Relaxation training, PDN , 76–77 (PMR) Restless legs syndrome (RLS) , 147 Poly ADP-ribose polymerase (PARP) , 130 Review Pregabalin , 52, 53, 56 antidepressants , 177 Pressure palsies chronic neuropathic pain , 71 carpal tunnel syndrome , 163 healthcare providers , 42 diagnosis , 164 “image imprinting” , 75 ulnar nerve and isolated nerve entrapments, relaxation methods , 77 163–164 RLS. See Restless legs syndrome (RLS) Prevention, PDN hyperglycaemia and glycometabolic control , 42–44 S insulin therapy , 45 SAE. See Serious adverse events (SAE) pathologic condition , 42 Safety, PDPN Progressive muscle relaxation (PMR) , 91 education and health system , 143 Protein kinase C (PKC) , 128 examination , 142 Proximal motor neuropathy. See Amyotrophy fall risk , 143–144 PSQI. See Pittsburgh sleep quality index polypharmacy , 144–145 (PSQI) preventive measures , 143 Psychological treatment Screening DPN , 41–42 ACT , 75–76 SCS. See Spinal cord stimulation (SCS) CBT , 73–74 Selective serotonin norepinephrine reuptake graded exposure , 76 inhibitors (SSNRIs) , 124 hypnosis , 77 Selective serotonin reuptake inhibitors “image imprinting” , 75 (SSRIs) , 123–124, 175 204 Index

Serious adverse events (SAE) , 101 TCAs , 123 Serotonin-norepinephrine reuptake inhibitors topical lidocaine , 126 (SNRIs) , 175, 177 Sleep impact, PDPN , 147 T , 147 Tai Chi , 66 painful DPN , 147 Topical analgesics, DPN PSQI , 147 capsaicin cream , 183–184 RLS , 147 GTN spray , 183 Small fi ber neuropathy , 160 isosorbide dinitrate spray , 183 Small fi ber symptoms , 30 Traditional Chinese Medicine (TCM) , 86, 88 Small fi bre tests , 30, 31 Tramadol hydrochloride , 54–55 SNRIs. See Serotonin-norepinephrine reuptake Tramodal , 181 inhibitors (SNRIs) Transcutaneous electrical nerve stimulation Spinal cord (TENS) , 56, 65 autopsy studies , 19 Transient receptor potential vanilloid receptor disinhibition , 21 1 (TRPV-1) , 98, 99 sensitization , 20 Tricyclic antidepressants (TCAs) , 51–52, 123, Spinal cord stimulation (SCS) 131, 174–177 acetylcholine and GABA , 96 TRPV-1. See Transient receptor potential chronic pain , 96 vanilloid receptor 1 (TRPV-1) complications , 98 Truncal radiculopathy , 163 DPN patients , 187 Type 2 diabetes mellitus (T2DM) , 141 Melzack–Wall gate theory , 96, 97 procedure description , 97–98 VAS , 96 V SSNRIs. See Selective serotonin VAS. See Visual analog scale (VAS) norepinephrine reuptake inhibitors VASPI. See Visual analog scale of pain (SSNRIs) intensity (VASPI) SSRIs. See Selective serotonin reuptake Vibration perception thresholds (VPT) , inhibitors (SSRIs) 30, 31 Symmetrical neuropathies Visual analog scale (VAS) , 42, 96 acute painful (see Acute painful Visual analog scale of pain intensity neuropathy) (VASPI) , 100 DPN ( see Diabetic peripheral neuropathy Vitamin B12 de fi ciency , 92 (DPN)) VPT. See Vibration perception thresholds small- fi bre , 160 (VPT) Symptomatic treatments calcium channel modulators , 124–125 capsaicin , 126 W gabapentin–venlafaxine , 127 Work productivity , 114–115 glycerol trinitrate , 126–127 nitric oxide , 126 / , 127–128 Y opioids , 125–126 Yoga , 66 –gabapentin , 127 RCTs , 126 SSNRIs , 124 Z SSRIs , 123–124 Ziconotide , 100, 101